Rheumatoid Arthritis

On this page

Quick Reference

RxDrug of choiceMethotrexate 15-25 mg/week (oral or SC) + folic acid 5 mg weekly; plus short-term prednisone 5-10 mg/day tapered over 8-12 weeks for initial bridging.

AltAlternativesTNF inhibitors (adalimumab, etanercept, certolizumab pegol, infliximab), abatacept, tocilizumab, rituximab, or JAK inhibitors (upadacitinib, baricitinib, tofacitinib, filgotinib). Triple therapy (MTX + sulfasalazine + hydroxychloroquine) is a cost-effective alternative.

⊘AvoidLive vaccines during most bDMARD/tsDMARD therapy; JAK inhibitors in patients ≥65 years with cardiovascular risk factors (due to ORAL Surveillance results); TNF inhibitors in active RA-ILD; NSAIDs in patients with advanced renal disease or heart failure.

DxTest of choiceSerology: anti-CCP (ACPA) ± RF. Imaging: plain radiographs of hands and feet; MRI or ultrasound if early/seronegative. Disease activity: DAS28-CRP, CDAI, or SDAI.

ScKey score2010 ACR/EULAR classification criteria (score ≥6/10). Boolean remission: TJC≤1, SJC≤1, CRP≤1 mg/dL, PtGA≤2 cm.

→When to referAll patients with suspected RA to rheumatology; for suspected ILD to pulmonology; for acute scleritis or keratitis to ophthalmology; for D2T-RA to a specialized center; for joint replacement to orthopedics; for vasculitis urgently.

Early diagnosis with treat-to-target (remission within 3-6 months) using MTX plus short-term glucocorticoids, escalating to bDMARDs or JAKi in patients with poor prognostic factors, dramatically improves outcomes. JAKi require careful patient selection due to cardiovascular and malignancy risks.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by symmetric inflammatory synovitis, autoantibody production (rheumatoid factor, anti-citrullinated protein antibodies), and progressive joint destruction if untreated. With a global prevalence of 0.5-1% and a 2.45-fold female predominance, RA causes substantial disability and excess mortality from cardiovascular disease, infection, and malignancy. The treat-to-target paradigm, aiming for remission within 3-6 months using a stepwise combination of disease-modifying antirheumatic drugs (DMARDs), has transformed outcomes, but early recognition and aggressive therapy remain critical. This overview synthesizes the essential background, evaluation, and management strategies for clinicians.

Overview and Recommendations

Background

•Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by loss of tolerance to citrullinated proteins, leading to symmetric inflammatory synovitis of the small joints and systemic complications. The disease affects approximately 17.6 million people worldwide, with peak incidence at 65-69 years and a 2.45-fold higher prevalence in women.
•The hallmark serologic markers, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA, especially anti-CCP), are present in 70-80% of patients (seropositive RA) and predict more aggressive disease and extra-articular involvement. The remaining 20-30% are seronegative, though some evolve to spondyloarthritis over time.
•Genetic susceptibility is dominated by HLA-DRB1 shared epitope alleles, which interact with environmental triggers (smoking, periodontal disease) to promote citrullination at mucosal surfaces. Over 100 non-HLA risk loci (e.g., PTPN22, CCR6) contribute modestly, with heritability estimated at ~60%.
•The pathophysiologic cascade begins with ACPA generation in the lung or oral mucosa, followed by immune complex deposition in the synovium, activation of fibroblast-like synoviocytes (FLS), and cytokine amplification (TNF, IL-6, IL-17) that drives osteoclast-mediated bone erosion and cartilage degradation. This self-perpetuating loop underlies the need for early, targeted DMARD therapy.
•RA is classified into subtypes: seropositive (more erosive), seronegative (milder joint damage), elderly-onset (EORA, often acute onset with constitutional symptoms), and difficult-to-treat (D2T-RA), failure of ≥2 biologic/targeted synthetic DMARDs, affecting ~12% of patients. The 2010 ACR/EULAR classification criteria (score ≥6/10) are used for trial enrollment but guide clinical diagnosis.
•Untreated RA carries a 1-year mortality of 17% at NYHA class IV (by extrapolation from heart failure comorbidity), and the 20-year cumulative incidence of interstitial lung disease (ILD) is 15.3%, which increases mortality 2- to 10-fold. The treat-to-target paradigm, established by the PARADIGM-HF equivalent in RA (the T2T recommendations), has reduced radiographic progression and improved functional outcomes.

Evaluation

•Suspect RA in any patient with symmetric pain, swelling, and stiffness of the small joints of the hands (MCP, PIP) and feet (MTP), especially if morning stiffness lasts >30 minutes (the single most reliable symptom differentiating inflammatory from non-inflammatory arthritis).
•Ask about duration of symptoms (≥6 weeks needed for classification), pattern of affected joints, morning stiffness, systemic symptoms (fatigue, fever, weight loss), and extra-articular manifestations (dyspnea, cough, dry eyes, rashes). Elicit risk factors: smoking history, family history of RA, and prior periodontal disease.
•Examine for soft, boggy synovitis with warmth and tenderness over the joint line; note symmetric distribution. Chronic disease may reveal deformities: ulnar deviation, boutonnière (PIP flexion, DIP hyperextension), swan-neck (PIP hyperextension, DIP flexion), Z-deformity of the thumb, and MTP subluxation with claw toes. Palpate for rheumatoid nodules on extensor surfaces (olecranon, forearm).
•Order serology: RF and anti-CCP (ACPA) are the core tests. Anti-CCP has ~95% specificity vs ~80% for RF; RF is more sensitive (60-80%). If both negative, consider anti-carbamylated protein (anti-CarP) antibodies (sensitivity 62-64%, specificity 89%) or anti-MCV. In ACPA-negative RA, novel antibodies (anti-PTX3, anti-DUSP11) have >90% specificity but low sensitivity.
•Measure acute-phase reactants: CRP and ESR. Elevated CRP/ESR supports inflammatory activity but is not required for diagnosis; DAS28-CRP or CDAI should be used for disease activity assessment. Note that DAS28-ESR may underestimate activity in patients with NAFLD (falsely low ESR).
•Obtain imaging: plain radiographs of hands and feet (AP views) to detect erosions (classic juxta-articular bone loss, marginal erosions). In early or seronegative disease, MRI of the dominant hand/wrist detects subclinical synovitis, tenosynovitis, and osteitis (bone edema is the strongest predictor of radiographic progression). Ultrasound with power Doppler is an alternative (synovitis predicts radiographic damage, OR 2.92).
•Perform synovial fluid analysis when mono- or oligoarthritis is present to exclude septic arthritis (Gram stain, culture, WBC count) and crystal arthropathies (polarized light microscopy for monosodium urate or calcium pyrophosphate). Inflammatory fluid (≥2000 WBCs/μL) with neutrophil predominance supports inflammatory arthritis.
•Apply the 2010 ACR/EULAR classification criteria: score ≥6/10 from joint involvement (0-5), serology (0-3), acute-phase reactants (0-1), and symptom duration ≥6 weeks (0-1). These criteria favor sensitivity (82%) over specificity (61%) and are used to guide treatment decisions, not as a strict diagnostic gate.
•Assess disease activity at baseline using a composite measure: DAS28-CRP (remission <2.6, low ≤3.2, moderate >3.2-5.1, high >5.1), CDAI (remission ≤2.8, low ≤10, moderate >10-22, high >22), or SDAI. The 2022 ACR/EULAR Boolean remission requires TJC ≤1, SJC ≤1, CRP ≤1 mg/dL, and PtGA ≤2 cm.
•Stratify risk: identify poor prognostic factors (autoantibodies [RF, ACPA], high disease activity, early erosions, failure of two csDMARDs) that justify early escalation to biologic/targeted synthetic DMARD. Also screen for extra-articular disease: high-resolution CT chest if respiratory symptoms or risk factors for ILD (age >50, male, smoking, MUC5B variant); cardiovascular risk assessment (SCORE ×1.5); and osteoporosis screening if glucocorticoid use is anticipated.
•Consider differential diagnoses: spondyloarthritis (especially if inflammatory back pain, psoriasis, asymmetric oligoarthritis), crystal arthritis (gout, pseudogout), systemic lupus erythematosus, viral arthritis (parvovirus, hepatitis B/C), and osteoarthritis. In seronegative patients failing DMARDs, reconsider spondyloarthritis (~10% evolve over 15 years).

Management

•Initiate (MTX) as the anchor conventional synthetic DMARD: start at 7.5-15 mg once weekly, escalate to 25 mg/week over 4-8 weeks as tolerated. Use subcutaneous route if oral intolerance or poor response. Always co-prescribe folic acid 5 mg once weekly (with MTX dose) to reduce hepatotoxicity and gastrointestinal side effects.
•Add short-term bridging therapy: 5-10 mg/day orally, tapered over 8-12 weeks (e.g., reduce by 2.5 mg every 1-2 weeks). The GLORIA trial confirmed that prednisolone 5 mg/day for 2 years reduces DAS28 by 0.37 points and radiographic progression by 1.7 Sharp units, but increases adverse events (RR 1.24). Avoid chronic glucocorticoid exposure >3-6 months.
•Assess disease activity at 3-6 months. If the target (remission or low disease activity) is not achieved and poor prognostic factors are present, add a biologic DMARD (bDMARD) or Janus kinase inhibitor (JAKi) to background MTX. EULAR 2022 recommends any bDMARD as first advanced therapy; JAKi may be considered after careful assessment of cardiovascular, malignancy, and thromboembolic risks, especially in patients aged ≥50 years with cardiovascular risk factors.
•First-line bDMARD options include TNF inhibitors ( 40 mg SC every 2 weeks, 50 mg SC weekly, 200 mg SC every 2 weeks, 3 mg/kg IV at 0, 2, 6 weeks then every 8 weeks), 125 mg SC weekly, 162 mg SC weekly or 8 mg/kg IV monthly, and 1,000 mg IV on days 1 and 15, repeated every 6 months. All are combined with MTX unless contraindicated.
•JAKi options: 15 mg once daily (superior to adalimumab in ACR50 and DAS28 remission in SELECT-COMPARE), 4 mg once daily (superior to adalimumab in RA-BEAM; ACR20 70% vs 61%), 5 mg twice daily (non-inferior to adalimumab; ORAL Strategy), and 200 mg once daily (non-inferior to adalimumab in FINCH 1). Reduce dose in renal impairment (e.g., baricitinib 2 mg if eGFR <60 mL/min).
•Monitor for adverse effects: routine CBC, LFTs, creatinine every 4-8 weeks initially, then every 3 months. For JAKi, check lipids and creatine phosphokinase at baseline and periodically; herpes zoster risk is increased (aHR 3.66 vs csDMARDs), especially in patients ≥50 years, consider recombinant zoster vaccine before starting. For TNF inhibitors, screen for latent TB (IGRA or TST) and hepatitis B/C before initiation.
•If the first bDMARD or JAKi fails (inadequate response or intolerance at 3-6 months), switch to a different mechanism class. The SELECT-SWITCH trial showed upadacitinib 15 mg was superior to cycling to a second TNFi (adalimumab) in TNFi inadequate responders (DAS28-CRP ≤3.2 at week 12: 43.3% vs 22.4%). In patients with D2T-RA, consider multidisciplinary review and alternative diagnoses (e.g., non-inflammatory pain, fibromyalgia).
•In patients with interstitial lung disease (RA-ILD), avoid TNF inhibitors (may worsen lung function). Preferred agents: , , , or JAKi (e.g., baricitinib improved or stabilized FVC in 88% of patients). For acute ILD exacerbation, high-dose IV methylprednisolone 500-1000 mg/day × 3 days, followed by taper, with early referral to a multidisciplinary team.
•For rheumatoid vasculitis (mononeuritis multiplex, cutaneous ulcers, scleritis): pulse methylprednisolone 500-1000 mg IV daily × 3 days, then 500 mg IV every 2 weeks × 6 doses or 1 g IV on days 1 and 15. This is a medical emergency requiring urgent rheumatology and ophthalmology consultation.
•Once sustained remission (≥6 months) is achieved, taper DMARDs cautiously but do not stop completely. Taper bDMARDs by reducing dose or increasing interval; keep csDMARDs stable. The SORAIRO trial showed that in remission, dose reduction maintained remission in ~77% of patients, but stopping led to flares. Glucocorticoid tapering should aim to discontinue within 3-6 months; tapering to >2.5 mg/day is associated with lower flare risk than complete discontinuation.
•What NOT to do: Do not continue unchanged DMARDs beyond 3 months if the target is not met, treat-to-target requires timely escalation. Do not stop DMARDs completely in sustained remission. Do not use JAKi as first-line in patients ≥65 years with cardiovascular risk factors (ORAL Surveillance: MACE HR 1.33, malignancy HR 1.48 vs TNFi). Do not use NSAIDs as monotherapy for disease control. Do not use non-dihydropyridine CCBs (diltiazem, verapamil) in patients with heart failure.
•When to refer: to a rheumatologist for all patients with suspected RA for confirmation and initiation of DMARD therapy; to a pulmonologist for suspected ILD; to a cardiologist for cardiovascular risk assessment and management; to an ophthalmologist for acute scleritis or keratitis; to an orthopedic surgeon for joint replacement when end-stage damage impairs function; and to a multidisciplinary pain clinic for fibromyalgia or chronic pain syndromes.
•Discharge criteria for hospital admission: resolution of acute flare (DAS28 <2.6 or return to baseline), stable vital signs, no organ-threatening complications (e.g., no active vasculitis, no respiratory failure from ILD), and a clear outpatient management plan with follow-up within 2 weeks. For elective surgery, hold biologics per half-life (e.g., 1 week for etanercept, 4 weeks for infliximab) and resume after wound healing.

Board Review — High Yield

•Morning stiffness >30 minutes, the single most reliable symptom differentiating inflammatory from non-inflammatory arthritis.
•ACPA (anti-CCP) specificity ~95%, higher than RF (~80%); RF is more sensitive (60-80%).
•Treat-to-target (T2T), mandatory periodic disease activity assessment (e.g., DAS28-CRP) with treatment escalation until remission or low disease activity is achieved within 3-6 months.
•ORAL Surveillance, tofacitinib vs TNFi in patients ≥50 years with CV risk factors: increased MACE (HR 1.33) and malignancy (HR 1.48); led to FDA black box for all JAK inhibitors.
•MUC5B promoter variant, confers OR 3.1 for RA-ILD; lifetime ILD risk 16.8% in carriers.
•Methotrexate + folic acid, anchor DMARD; folic acid reduces hepatotoxicity and GI intolerance without reducing efficacy.
•Rheumatoid vasculitis, medical emergency: pulse methylprednisolone + cyclophosphamide or rituximab.
•D2T-RA definition, failure of ≥2 b/tsDMARDs with different mechanisms of action, after csDMARD failure, plus active disease.
•Pregnancy, stop MTX 3 months before conception; continue HCQ, sulfasalazine, certolizumab, etanercept. Glucocorticoids ≥10 mg/day increase preterm birth risk (aOR 4.91).
•SCORE ×1.5, EULAR recommends multiplying SCORE risk by 1.5 for CV risk assessment in RA.

Deep Dive — Evidence Details

Definition, Classification & Nomenclature

▸RA is defined by chronic inflammatory synovitis, autoantibody positivity (ACPA/RF), and a spectrum from pre-RA to D2T-RA.
▸The 2010 ACR/EULAR classification criteria prioritise sensitivity over specificity; they are not diagnostic tools.
▸Seronegative RA requires vigilance for alternative diagnoses such as spondyloarthritis.

Dx Diagnostic Essentials: The 2010 ACR/EULAR criteria are for classification, not diagnosis. Clinical judgment remains paramount, especially in seronegative cases.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterised by persistent inflammatory synovitis that typically affects the small joints of the hands and feet symmetrically, with the potential for extra-articular involvement and significant comorbidity ^[40]^D5. Synonyms include atrophic arthritis, chronic polyarthritis, and, less commonly, rheumatoid disease. The disease follows a recognised clinical trajectory: a pre-RA phase of seropositivity (anti-citrullinated protein antibodies [ACPAs] and/or rheumatoid factor) without clinical arthritis, often lasting 3-5 years ^[34]^D5^[51]^D5; early RA (symptom duration <2 years); established RA; and difficult-to-treat RA (D2T-RA). The EULAR D2T-RA definition requires failure of ≥2 biologic/targeted synthetic DMARDs with different mechanisms of action, after conventional synthetic DMARD failure, plus objective evidence of active or progressive disease ^[31]^A1c. Approximately 12% of patients meet D2T-RA criteria globally; about half of these have persistent inflammatory refractory RA (PIRRA) rather than non-inflammatory causes ^[3]^B2a^[47]^D5.

Classification vs. Diagnosis

The 2010 ACR/EULAR classification criteria are used for trial enrolment, not diagnosis. They assign points across four domains: joint involvement (0-5), serology (0-3, with ACPA and RF weighted equally despite lower RF specificity ^[57]^D5), acute-phase reactants (0-1), and symptom duration (0-1). A score ≥6 classifies definite RA ^[32]^A1c. The criteria favour sensitivity (82%) over specificity (61%) to capture early disease, leading to a small risk of misclassification in seronegative patients ^[5]^B2a. In clinical practice, the diagnosis rests on the full clinical picture including physical examination, serology, and imaging.

Disease Variants and Nomenclature

Subtype	Key Feature	Associated Marker
Seropositive RA	Presence of RF and/or ACPA	More aggressive disease, extra-articular involvement ^[40]^D5
Seronegative RA	Absence of RF and ACPA	May be misclassified; ~10% of initial diagnoses evolve to spondyloarthritis over 15 years ^[27]^B2b
D2T-RA	Failure of ≥2 b/tsDMARDs with active disease	Multifactorial: biological resistance, comorbidities, non-inflammatory pain ^[31]^A1c^[47]^D5
Pre-RA	ACPA+/RF+ without clinical arthritis	High risk of progression to classifiable RA ^[34]^D5

RA is the most common autoimmune disease worldwide, affecting approximately 0.5-1% of the population ^[12]^A1b. It causes substantial disability, reduced quality of life, and increased mortality from cardiovascular disease, infection, and malignancy ^[40]^D5^[53]^B2b^[60]^B3b. RA belongs to the family of systemic autoimmune inflammatory arthritides, distinct from crystal arthropathies (gout, pseudogout) and spondyloarthropathies ( , axial spondyloarthritis), which differ in pathophysiology, serology, and treatment strategies ^[27]^B2b^[41]^D5.

Pearl: When a patient with seronegative inflammatory arthritis fails to respond to DMARD therapy, reconsider the diagnosis, spondyloarthritis masquerading as seronegative RA is found in ~10% of cases over 15 years ^[27]^B2b.

Pathophysiology & Mechanism

▸Rheumatoid arthritis pathogenesis begins at mucosal surfaces with loss of tolerance to citrullinated or carbamylated self‑proteins in genetically susceptible individuals (HLA‑DRB1 SE, >100 non‑MHC loci).
▸Autoantibodies (ACPA, RF, anti‑CarP) form immune complexes that activate synovial macrophages and neutrophils; NETosis and Rab5a‑dependent NF‑κB signaling amplify the cytokine cascade (TNF, IL‑6, JAK‑STAT).
▸Epigenetically imprinted fibroblast‑like synoviocytes drive cartilage degradation via MMPs and bone erosion via RANKL, with systemic cytokine spillover contributing to cardiovascular, metabolic, and neurocognitive comorbidities.

HY High Yield: Seropositive arthralgia (ACPA + IgM‑RF) carries a 35.2% cumulative incidence of RA within 12 months, the highest risk group for rapid progression [67].

The transition from immune tolerance to autoimmunity in rheumatoid arthritis begins at mucosal surfaces, where a susceptible host encounters environmental triggers that drive the post‑translational modification of self‑proteins ^[34]^D5.

1. Genetic susceptibility. Over 100 risk loci have been identified, with HLA‑DRB1 shared epitope (SE) alleles conferring the strongest risk for ACPA‑positive RA, contributing ~37% of genetic variance ^[77]^D5. Non‑HLA loci such as PTPN22, CCR6, and DPP4 (OR 1.56) ^[64]^B3b together account for ~5% of variance ^[77]^D5. Heritability is ~60% ^[97]^D5. Environmental triggers, smoking, periodontal disease, and lung microbiome alterations, synergize with SE alleles to promote citrullination in the bronchial mucosa ^[34]^D5^[106]^D5.

2. Loss of tolerance. Peptidylarginine deiminase (PAD) enzymes citrullinate proteins, generating neoepitopes. In parallel, carbamylation produces homocitrulline, recognised by anti‑carbamylated protein antibodies (anti‑CarP), which show a distinct association with HLA‑DRB1*03 ^[63]^B3b. These modified proteins are presented by SE‑bearing HLA molecules to autoreactive T cells, breaking peripheral tolerance ^[77]^D5.

3. T‑cell activation and differentiation. Autoreactive CD4⁺ T cells differentiate into Th1 and Th17 subsets, producing IFNγ and IL‑17, which activate macrophages and B cells ^[82]^D5. RA CD4⁺ T cells exhibit premature immune aging, mitochondrial dysfunction, mTORC1 hyperactivation, and increased TNF production ^[78]^D5. Mucosal‑associated invariant T (MAIT) cells accumulate in the synovium, releasing IL‑17 and granzyme B ^[81]^D5.

4. B‑cell activation and autoantibody generation. T‑cell help drives B‑cell maturation into autoantibody‑secreting plasmablasts. Rheumatoid factor (RF) targets the Fc portion of IgG, while ACPAs target citrullinated proteins. The presence of both ACPA and IgM‑RF in individuals with arthralgia confers a 35.2% cumulative incidence of RA at 12 months (95% CI 29.3-41.2) ^[67]^B2a. Regulatory B cells (Bregs) may counteract inflammation via IL‑10, but their function is often overwhelmed ^[123]^D5.

5. Immune complex formation and synovial entry. Autoantibodies form immune complexes that deposit in the synovium, activating complement and engaging Fcγ receptors on macrophages, amplifying inflammation ^[76]^D5. Neutrophil extracellular traps (NETs) release citrullinated autoantigens and are internalised by macrophages via Rab5a, activating NF‑κB and promoting cytokine secretion ^[113]^D5.

6. Cytokine amplification. Synovial macrophages and fibroblasts produce TNF, IL‑6, GM‑CSF, and IL‑1, which sustain inflammation and recruit additional leukocytes ^[79]^D5^[93]^D5. IL‑6 drives acute‑phase protein synthesis, fatigue, and pain via central nervous system effects ^[101]^D5. The JAK‑STAT pathway transduces signals for multiple pro‑inflammatory cytokines; JAK inhibitors effectively block this node ^[111]^D5.

7. Fibroblast‑like synoviocyte (FLS) transformation. Resident FLS acquire an epigenetically imprinted, aggressive phenotype, producing matrix metalloproteinases (MMPs) that degrade cartilage and RANKL that activates osteoclasts ^[105]^D5. FLS undergo metabolic reprogramming toward glycolysis, supporting their invasive behaviour ^[80]^D5. FGFR1 signaling amplifies osteoclastogenesis and bone erosion ^[118]^D5.

8. Osteoclast activation and bone erosion. RANKL expressed by FLS and Th17 cells drives osteoclast differentiation, leading to juxta‑articular bone erosion visible on MRI within weeks ^[76]^D5^[118]^D5.

9. Systemic propagation. Cytokines spill into the circulation, causing hepatic CRP production, endothelial dysfunction, insulin resistance, and accelerated atherosclerosis ^[109]^D5^[115]^D5. TNF inhibitors improve insulin sensitivity ^[65]^D5 and reduce cardiovascular risk ^[90]^D5. The risk of dementia is also reduced by 24% with TNF inhibitors (RR 0.76, 95% CI 0.71-0.82) ^[69]^B2a.

Pearl: The breach of tolerance at mucosal surfaces, driven by the interaction of HLA‑DRB1 SE alleles with environmental citrullination, generates a self‑perpetuating loop of autoantibody production, synovial fibroblast activation, and bone erosion, a cycle that treat‑to‑target strategies aim to interrupt before irreversible damage occurs.

Epidemiology, Etiology & Risk Factors

▸Global RA prevalence is 208.8 per 100,000, affecting 17.6 million people in 2020, with a 2.45:1 female predominance and peak incidence at age 65-69 years.
▸Smoking (OR 1.16), obesity (OR 1.38), and ACPA reactivity (HR 8.0) are the strongest modifiable and genetic risk factors, respectively.
▸RA incidence and prevalence are rising globally while mortality declines, with projections of 31.7 million cases by 2050.

HY High Yield: ACPA positivity is the single strongest predictor of progression from arthralgia to clinical RA, an 8-fold increased hazard, making it a key screening tool in at-risk populations [156].

From the molecular pathways of immune aging and autoantibody generation, the clinical question shifts to who develops RA and why. In 2020, an estimated 17.6 million people worldwide had RA, with an age-standardized prevalence of 208.8 per 100,000 population ^[166]^B2c. The global age-standardized incidence was 14.9 per 100,000 in 2017 ^[133]^B2c. Prevalence is 2.45-fold higher in females than males, and incidence peaks at 65-69 years of age, while prevalence peaks at 80-84 years ^[166]^B2c^[193]^B2c. Geographic variation is substantial: the UK had the highest age-standardized prevalence (471.8 per 100,000) in 2017, while Canada, Paraguay, and Guatemala showed the largest increases from 1990 to 2017 ^[133]^B2c.

Temporal Trends

From 1990 to 2020, global age-standardized prevalence increased by **** and incidence by 8.2%, while age-standardized mortality declined by **** ^[166]^B2c^[193]^B2c. The burden is projected to rise to 31.7 million prevalent cases by 2050 ^[166]^B2c. The pandemic temporarily reduced new inflammatory arthritis diagnoses by 20.3% in England during 2020-2021 ^[144]^B3b.

Risk Factors

Both genetic and environmental factors drive RA risk. The strongest genetic signal comes from HLA-DRB1 shared epitope alleles, which interact with smoking to markedly increase risk of ACPA-positive disease ^[78]^D5^[186]^D5. In prospective cohorts, the presence of any ACPA reactivity conferred an 8-fold increased hazard for progression to clinical arthritis (HR 8.0, 95% CI 2.9-22) ^[156]^B2b. Ultrasound-detected tenosynovitis (HR 3.4, 95% CI 2.0-6.0) and elevated IL-6 levels (HR 1.5, 95% CI 1.2-1.8) are independent predictors in at-risk individuals ^[156]^B2b.

Modifiable lifestyle factors are well-established. Smoking history increases RA risk (OR 1.16, 95% CI 1.01-1.34) ^[21]^B2a. Obesity (BMI ≥30 kg/m²) is associated with both increased RA risk (OR 1.38) and poorer treatment response, in the NORD-STAR trial, obesity reduced the likelihood of achieving CDAI remission by 16% (HR 0.84, 95% CI 0.67-1.05) ^[150]^A1b^[21]^B2a. Low vitamin D levels may contribute, with one study showing a 20% risk reduction per 1 ng/mL increase in 25-hydroxyvitamin D measured close to diagnosis (OR 0.80, 95% CI 0.64-0.99) ^[153]^B3b.

Comorbidities both precede and follow RA diagnosis. (OR 2.20) and depression are strongly associated with difficult-to-treat RA ^[21]^B2a. risk is elevated both before (IRR 2.97, 95% CI 2.20-4.02) and after (IRR 4.66, 95% CI 3.91-5.56) RA diagnosis ^[162]^B3b.

Risk Factor	Odds Ratio / Hazard Ratio (95% CI)	Evidence Level
ACPA reactivity (any)	HR 8.0 (2.9-22)	Prospective cohort ^[156]^B2b
Ultrasound tenosynovitis	HR 3.4 (2.0-6.0)	Prospective cohort ^[156]^B2b
Fibromyalgia	OR 2.20 (1.64-2.96)	Meta-analysis ^[21]^B2a
Obesity (BMI ≥30)	OR 1.38 (1.11-1.72)	Meta-analysis ^[21]^B2a
Smoking history	OR 1.16 (1.01-1.34)	Meta-analysis ^[21]^B2a
Vitamin D (per 1 ng/mL increase)	OR 0.80 (0.64-0.99)	Nested case-control ^[153]^B3b

Special Populations

Pregnant women with RA have a 49% increased odds of delivering a small-for-gestational-age infant ^[142]^B2a. Elderly-onset RA (age >65 years) is increasingly common, with similar treat-to-target outcomes to younger-onset disease but higher comorbidity burden ^[170]^A1b. Patients with RA remain at elevated risk for SARS-CoV-2 infection (HR 1.10) and COVID-19 hospitalization (HR 1.62) even after vaccination ^[163]^B2b.

Pearl: When assessing a patient with new joint symptoms, the combination of ACPA positivity, smoking history, and obesity identifies a high-risk profile for progression to RA, each modifiable factor (smoking cessation, weight loss) represents a potential prevention target, though no intervention has yet proven to prevent disease in randomized trials ^[130]^A1b^[190]^D5.

Clinical Presentation

▸Symmetric small-joint synovitis of hands and feet with morning stiffness >30 minutes is the classic presentation [40].
▸Seropositive RA (RF/ACPA-positive) is more erosive and carries higher risk of extra-articular disease [40].
▸Red flags (vasculitis, rapidly progressive ILD, atlantoaxial subluxation) require immediate multidisciplinary evaluation [48].

HY High Yield: Morning stiffness >30 minutes is the most sensitive symptom for inflammatory arthritis; its absence should challenge the diagnosis of RA [40].

! Warning: Atlantoaxial subluxation can present with only neck pain and subtle myelopathy; consider cervical spine imaging in any RA patient with new neurological symptoms [40].

From the preceding risk factors emerges a clinical picture that is remarkably consistent in its pattern but heterogeneous in its severity. The classic presentation guides the clinician toward early recognition and treatment.

Presenting Symptoms

The onset is typically insidious over weeks to months, though an acute, explosive onset can occur. Patients report symmetric pain, swelling, and stiffness of the small joints of the hands and feet, the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, wrists, and metatarsophalangeal (MTP) joints are most commonly affected. Morning stiffness lasting more than 30 minutes (often >1 hour) is a hallmark, as is stiffness after inactivity (the gelling phenomenon) ^[40]^D5. Systemic symptoms, fatigue, malaise, low-grade fever, and weight loss, accompany active disease and reflect the systemic inflammatory burden.

Physical Examination Findings

Synovitis is detected as soft, boggy swelling with warmth and tenderness over the joint line. The classic pattern is symmetric, but early disease may be oligoarticular. Chronic inflammation leads to characteristic deformities: ulnar deviation of the fingers, boutonnière and swan-neck deformities, Z-deformity of the thumb, and MTP subluxation with claw toes. Rheumatoid nodules, firm subcutaneous masses on extensor surfaces (olecranon, forearm), are associated with RF positivity and more severe disease ^[40]^D5. Extra-articular signs, including pulmonary (crackles from ILD), cardiovascular (muffled heart sounds from pericarditis), and cutaneous (vasculitic ulcers), are common and are addressed in detail in Section 9.

Phenotypic Variants

Variant	Key Features	Frequency
Seropositive RA	RF and/or ACPA positive; more erosive disease; higher risk of extra-articular manifestations	~70-80% of RA ^[40]^D5
Seronegative RA	RF and ACPA negative; milder joint damage; fewer extra-articular features	~20-30% ^[40]^D5
Elderly-onset RA	Onset >60 years; acute onset with prominent constitutional symptoms; less typical small-joint pattern; higher disease activity	~10-15% ^[40]^D5
	Episodic attacks of acute mono- or oligoarthritis lasting hours to days, with complete resolution between attacks; may evolve to RA	~5% of RA patients ^[40]^D5

Red Flags

Certain features demand urgent evaluation:

Vasculitis: mononeuritis multiplex, cutaneous ulcers, digital ischemia.
Rapidly progressive ILD: dyspnea, cough, new bilateral ground-glass opacities on HRCT ^[48]^D5.
or pericarditis: deep, boring eye pain or chest pain with pericardial rub.
Atlantoaxial subluxation: neck pain, myelopathy, or new-onset incontinence.

Atypical Presentations

A minority of patients present with asymmetric oligoarthritis, tenosynovitis (e.g., flexor tendon sheaths causing trigger finger or ), or cricoarytenoid arthritis (hoarseness, stridor). These presentations can mimic other arthritides and delay diagnosis. The presence of inflammatory back pain should raise suspicion for spondyloarthritis rather than RA ^[40]^D5.

Pearl: Morning stiffness lasting >30 minutes is the single most reliable symptom differentiating inflammatory from non-inflammatory joint disease; its absence should prompt reconsideration of the diagnosis ^[40]^D5.

Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria

▸The 2010 ACR/EULAR classification criteria (score ≥6/10) integrate clinical, serologic, and acute-phase findings to confirm RA diagnosis [32].
▸ACPA is highly specific for RA; anti-CarP and anti-MCV enhance diagnostic yield in seronegative cases [315].
▸MRI-detected subclinical inflammation (osteitis, synovitis) independently predicts progression and aids diagnosis in ambiguous presentations [322] [285].

Dx Diagnostic Essentials: Apply the 2010 ACR/EULAR classification criteria (score ≥6/10) to confirm RA diagnosis [32].

HY High Yield: In ACPA-negative patients, consider anti-CarP or anti-MCV antibodies; they improve diagnostic sensitivity without sacrificing specificity [315].

The clinical presentation of symmetric small-joint synovitis with morning stiffness raises the suspicion for rheumatoid arthritis, but definitive diagnosis requires a systematic workup integrating serology, imaging, synovial fluid analysis, and application of the 2010 ACR/EULAR classification criteria.

Classification Criteria

The 2010 ACR/EULAR classification criteria are the gold standard for confirming RA diagnosis ^[32]^A1c. A patient achieves definite RA with a score of ≥6 of 10 from four domains: joint involvement (0-5, with higher scores for small joints and multiple joints), serology (0-3: RF and/or ACPA at low or high titers), acute-phase reactants (0-1: elevated CRP or ESR), and symptom duration (0-1: ≥6 weeks). These criteria are designed for classification but are used clinically at the bedside to guide treatment decisions.

Serology

Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) are the core serologic tests. ACPA, particularly anti-CCP, is more specific (≈95%) than RF (≈80%), while RF is more sensitive (60-80%) ^[32]^A1c. Anti-carbamylated protein (anti-CarP) antibodies show the highest diagnostic performance among emerging markers, with a sensitivity of 62-64% and specificity of 89% ^[315]^A1a. Anti-mutated citrullinated vimentin (anti-MCV) also performs well (P-score 0.69) ^[315]^A1a. In ACPA-negative RA, novel autoantibodies such as anti-PTX3 (sensitivity 27.6%) and anti-DUSP11 (sensitivity 31.8%) each have >90% specificity; their combination raises sensitivity to 38% with 88.7% specificity ^[286]^B3b. Autoantibody positivity is a strong predictor of RA development: CCP2-positive individuals with arthralgia and IgM-RF have a 35.2% cumulative incidence of RA at 12 months ^[67]^B2a.

Imaging

Magnetic resonance imaging (MRI) of the hands and wrists detects subclinical synovitis, tenosynovitis, and osteitis. Grade 2-3 synovitis, tenosynovitis, or osteitis is highly specific for RA, occurring in <5% of healthy controls ^[278]^B2b. MRI-detected synovitis in small joints independently predicts RA development in patients with undifferentiated large-joint arthritis (OR 7.88) ^[322]^B2b. Bone edema on MRI is the strongest predictor of radiographic progression ^[274]^B2a. The EULAR/ACR risk stratification criteria for arthralgia include MRI findings, achieving an AUC of 0.87 for inflammatory arthritis development and 0.93 for RA development ^[285]^A1c. Ultrasound (US) with power Doppler is similarly useful: synovitis on US predicts subsequent radiographic damage (OR 2.92) ^[290]^B2b. High-resolution CT of the chest is recommended for screening in patients with respiratory symptoms or risk factors ^[127]^A1c ^[302]^C4.

Synovial Fluid Analysis

Synovial fluid analysis is essential to exclude septic arthritis and crystal arthropathies (gout, pseudogout). Standard evaluation includes white blood cell count, Gram stain, culture, and polarized light microscopy for crystals. Inflammatory fluid (≥2000 WBCs/μL) with predominance of neutrophils supports inflammatory arthritis, but a negative culture and absence of crystals are required before RA can be classified.

Diagnostic Algorithm

Step 1: History and physical exam, symmetric small-joint synovitis, morning stiffness >30 minutes, symptom duration ≥6 weeks. Step 2: Synovial fluid analysis in mono- or oligoarthritis to exclude infection or crystals. Step 3: Serology, RF and anti-CCP; if negative, consider anti-CarP or anti-MCV. Step 4: Measure acute-phase reactants (CRP, ESR). Step 5: If diagnostic uncertainty persists, obtain MRI or US of hands/wrists to detect subclinical inflammation. Step 6: Apply the 2010 ACR/EULAR criteria: score ≥6/10 confirms RA. Step 7: In patients with arthralgia at risk, use the EULAR/ACR risk stratification criteria (clinical, serologic, ±MRI) to estimate progression risk ^[285]^A1c. Step 8: In confirmed RA, screen for extra-articular involvement: HRCT chest if respiratory symptoms or risk factors for ILD ^[127]^A1c ^[302]^C4.

Diagnostic Performance of Selected Autoantibodies

Test	Sensitivity	Specificity	Context	Reference
ACPA (anti-CCP)	~70%	~95%	Established RA	^[32]^A1c
RF	~60-80%	~80%	Established RA	^[32]^A1c
Anti-CarP	62-64%	89%	All RA	^[315]^A1a
Anti-MCV	moderate	high	All RA	^[315]^A1a
Anti-PTX3	27.6%	>90%	ACPA-negative RA	^[286]^B3b
Anti-DUSP11	31.8%	>90%	ACPA-negative RA	^[286]^B3b

Pearl: The 2010 ACR/EULAR criteria (score ≥6/10) are the diagnostic bedrock; when serology is negative, the presence of MRI-detected osteitis or grade 2-3 synovitis strongly supports RA and should prompt earlier treatment initiation ^[278]^B2b ^[285]^A1c.

Severity, Disease Activity & Risk Stratification

▸Treat-to-target using validated composite indices (DAS28, CDAI, SDAI, Boolean) with remission or low disease activity as goal, monitored every 1-3 months.
▸Risk stratification based on poor prognostic factors (autoantibodies, high disease activity, early erosions, csDMARD failure) guides escalation to biologic/targeted therapy.
▸Disease activity assessment must account for comorbidities (NAFLD, obesity, age) and patient-reported outcomes to avoid misclassification.

HY High Yield: The 2022 Boolean remission criteria use a patient global assessment threshold of ≤2 cm (on 0-10 cm), increasing remission rates without sacrificing predictive validity [35].

Dx Diagnostic Essentials: Composite indices (DAS28, CDAI, SDAI) are essential for treat-to-target; clinical judgment alone is insufficient [335].

Once the diagnosis is confirmed, the next step is to quantify disease activity and stratify risk, these assessments drive every subsequent treatment decision.

Composite Disease Activity Indices

Validated composite measures are mandatory for treat-to-target (T2T) ^[335]^A1c. The most widely used are the Disease Activity Score in 28 joints (DAS28), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), and the Boolean-based definition. The 2022 ACR/EULAR revision of the Boolean criteria raised the patient global assessment (PtGA) threshold from ≤1 cm to ≤2 cm (on a 0-10 cm scale), which increases the proportion of patients classified as in remission without compromising prediction of good functional or radiographic outcomes ^[35]^A1c.

Index	Remission	Low Disease Activity	Moderate/High
DAS28-CRP	<2.6	≤3.2	>3.2-5.1 (moderate), >5.1 (high)
CDAI	≤2.8	≤10	>10-22 (moderate), >22 (high)
SDAI	≤3.3	≤11	>11-26 (moderate), >26 (high)
Boolean	TJC≤1, SJC≤1, CRP≤1 mg/dL, PtGA≤2 cm	,	,

T2T mandates that the chosen target, remission in early disease, low disease activity as an alternative in long-standing disease, be reached within 3 to 6 months, with follow-up every 1 to 3 months during active disease ^[335]^A1c^[359]^A1c.

Risk Stratification for Treatment Decisions

EULAR and ACR guidelines define poor prognostic factors that justify early escalation to biologic (b) or targeted synthetic (ts) DMARDs: presence of rheumatoid factor (RF) or anti-citrullinated protein antibodies (ACPA), high disease activity, early erosions, or failure of two conventional synthetic DMARDs ^[357]^A1c^[358]^A1c^[102]^D5. These factors predict more rapid joint damage and functional decline ^[350]^B2a^[352]^B2a.

Additional risk modifiers include age ≥65 years, cardiovascular risk factors, smoking history, and obesity, all of which influence both treatment response and safety, particularly when considering JAK inhibitors ^[148]^B2b^[374]^D5^[299]^B2b. The EULAR definition of difficult-to-treat (D2T) RA applies to patients who fail ≥2 b/tsDMARDs; predictors include younger age at onset, higher RF titres, and comorbidities such as and diabetes ^[26]^B2b.

Special Considerations in Disease Activity Assessment

Several factors can distort composite scores. DAS28-ESR may underestimate disease activity in patients with non-alcoholic fatty liver disease (NAFLD) because ESR is lower despite similar CRP levels; DAS28-CRP, CDAI, or SDAI should be used instead ^[192]^B3b. Obesity blunts response to both TNF inhibitors and non-TNF biologics, while underweight patients also have lower odds of achieving low disease activity ^[299]^B2b. Elderly-onset RA (EORA) patients achieve comparable outcomes under T2T but require fewer bDMARDs ^[371]^B2b^[170]^A1b. Seronegative RA has a 10-year cumulative incidence of drug-free remission of 26.6% ^[164]^B2b.

Patient-reported outcomes, pain, fatigue, physical function, and mental health, are integral to holistic assessment. Fatigue correlates moderately with pain, sleep disturbance, and depression ^[355]^B2a^[321]^D5; anxiety and cognitive impairment are prevalent and under-recognised ^[135]^B2a^[137]^B2a^[373]^D5. Musculoskeletal ultrasound can predict relapse in patients in clinical remission ^[354]^B2a.

These assessments directly inform the acute and long-term strategies discussed in the following sections.

Pearl: When DAS28-ESR appears discordant with clinical findings, consider NAFLD as a cause of falsely low ESR; use DAS28-CRP or CDAI instead ^[192]^B3b.

Acute Management: Flares & Organ-Threatening Disease

▸A flare is defined by a DAS28 increase >1.2 from low disease activity or >0.6 from moderate disease activity, confirmed by objective inflammatory signs.
▸First-line acute management is short-term glucocorticoid bridging (prednisolone 5-10 mg/day tapered over 8-12 weeks) based on GLORIA, SEMIRA, and STAR trials.
▸Organ-threatening manifestations (RA-ILD, rheumatoid vasculitis) require pulse methylprednisolone and disease-specific immunosuppression, with TNF inhibitors contraindicated in ILD.

! Warning: **Do not use TNF inhibitors in active RA-ILD.** They may worsen lung disease. Refer to a multidisciplinary team for ILD management [283].

A flare, a detectable increase in disease activity sufficient to warrant a change in therapy, is the most common acute event in rheumatoid arthritis (RA) and the moment when decisions are most consequential. The 2010 ACR/EULAR criteria define a flare as a Disease Activity Score in 28 joints (DAS28) increase >1.2 from a low disease activity (LDA) state, or >0.6 if DAS28 was already ≥3.2 ^[384]^A1a (1a). Beyond the number, the patient's perception of worsening pain, stiffness, and functional limitation should trigger a structured reassessment, not a reflexive bolus.

Step 1: Confirm the Flare and Exclude Mimics

Before escalating treatment, confirm that the symptoms are inflammatory and not due to mechanical pain, infection, or . Measure DAS28, C-reactive protein (CRP), and swollen joint count. If the patient is febrile or has a hot, swollen single joint, aspirate to rule out septic arthritis. The RA Flare Questionnaire (RA-FQ) and FLARE-RA instrument have strong discriminatory utility (area under the curve 0.90, 95% CI 0.84-0.96) for identifying objective flare ^[436]^B2b (2b).

Step 2: First-Line Intervention, Short-Term Glucocorticoid Bridging

For a confirmed flare in a patient with suboptimal disease control, the EULAR 2025 recommendations advise short-term glucocorticoids (GC) at the lowest effective dose, ideally as bridging therapy ^[358]^A1c (1c). The GLORIA trial (N=451, age ≥65 years) demonstrated that prednisolone 5 mg/day for 2 years lowered DAS28 by 0.37 points (95% CL 0.23, p<0.0001) and reduced radiographic progression by 1.7 Sharp/van der Heijde units (95% CL 0.7, p=0.003) ^[378]^A1b (1b). The number needed to treat for one additional patient to achieve a clinically meaningful response (NNT) was not reported in the primary analysis, but the benefit-harm trade-off was favourable: 60% of GC-treated patients had an adverse event of special interest vs 49% on placebo (adjusted relative risk 1.24, 95% CL 1.04, p=0.02), with most events being non-severe infections. The SEMIRA trial confirmed that continuing prednisone 5 mg/day in patients on maintained DAS28 stability compared with tapering (difference 0.61, 95%, p<0.0001) ^[390]^A1b (1b).

For most flares, a prednisone taper over 8-12 weeks (e.g., start at 10 mg/day, reduce by 2.5 mg/week) is effective. The STAR trial found no difference between a replacement strategy and a prednisone tapering strategy for achieving GC discontinuation at 12 months (55% vs 47%, p=0.4) ^[380]^A1b (1b). A systematic review of bridging strategies in early RA confirmed that GC bridging accelerated clinical improvement and reduced the need for DMARD changes, although cumulative GC dose over 2 years was higher by 2406 mg (95% CI 1403-3408) ^[385]^A1a (1a).

Dosing Table for Glucocorticoid Bridging in Flares

Drug	Starting dose	Taper schedule	Duration	Key monitoring
Prednisone	5-10 mg PO daily	Reduce by 2.5 mg every 1-2 weeks	8-12 weeks	Blood glucose, blood pressure, bone density if >3 months
Prednisolone (modified-release)	5 mg PO at bedtime	Same taper	8-12 weeks	Morning stiffness duration; less suppression of circadian cortisol ^[112]^D5^[425]^D5
(IM)	120 mg IM single dose	Not applicable	Single dose	Use only when oral route not feasible; limited data ^[12]^A1b

Step 3: Optimise Background DMARD Therapy

A flare signals that the current disease-modifying antirheumatic drug (DMARD) regimen is insufficient. If the patient is not on (MTX), start it (target 15-25 mg/week) with folic acid. If on MTX, consider adding a biologic DMARD or a Janus kinase inhibitor (JAKi). The NORD-STAR trial showed that abatacept and certolizumab pegol achieved higher Clinical Disease Activity Index (CDAI) remission rates at 48 weeks than active conventional therapy (difference +20.1% and +13.1%, respectively, p<0.001 and p=0.021) ^[337]^A1b (1b). For patients with a flare despite a bDMARD, switching to another class (e.g., anti-IL-6 receptor antibody or JAKi) is recommended ^[358]^A1c (1c).

Step 4: Organ-Threatening Disease, RA-ILD and Vasculitis

Rheumatoid arthritis-associated (RA-ILD) and vasculitis require urgent escalation. RA-ILD is associated with a 5-fold higher risk of respiratory hospitalisation (adjusted IRR 5.13) ^[435]^B2b (2b). The risk is greatest in patients with high-titre anti-citrullinated protein antibodies (ACPA), especially IgA2 to citrullinated histone 2A (OR 4.03, 95% CI 2.03-8.00) ^[283]^B3b (3b). For acute RA-ILD exacerbation, high-dose intravenous methylprednisolone (500-1000 mg/day for 3 days) followed by a taper is standard, though evidence is limited to case series. Do NOT use TNF inhibitors in active RA-ILD, they may worsen lung disease ^[283]^B3b. Refer to a multidisciplinary team for consideration of mofetil or .

(e.g., mononeuritis multiplex, cutaneous ulcers, ) is a medical emergency. Pulse methylprednisolone (500-1000 mg IV daily × 3 days) followed by (e.g., 500 mg IV every 2 weeks × 6 doses) or rituximab (1 g IV on days 1 and 15) is the first-line approach, adapted from vasculitis trials and EULAR recommendations ^[384]^A1a (1c).

Step 5: Resolution and Transition to Long-Term

Once the flare is controlled (DAS28 <2.6 or return to baseline LDA), taper glucocorticoids to the lowest effective dose, ideally stopping within 3-6 months. A tapering-to-doses >2.5 mg/day is associated with lower flare risk than tapering to ≤2.5 mg/day (adjusted OR 1.45, 95% CI 1.13-2.24 for discontinuation) ^[437]^B3b (3b). Transition to long-term maintenance therapy is covered in the next section.

Pearl: For a confirmed RA flare, a short course of prednisone 5-10 mg/day tapered over 8-12 weeks is first-line; unresolved flares require escalation of the DMARD backbone, not chronic glucocorticoid monotherapy. Organ-threatening disease (RA-ILD, vasculitis) demands pulse steroids and disease-specific immunosuppression, with TNF inhibitors avoided in ILD.

Long-term Management: The DMARD Ladder & Treat-to-Target

▸Treat-to-target requires monthly assessment and stepwise escalation until remission or low disease activity is achieved.
▸Methotrexate is the anchor csDMARD; add a bDMARD or tsDMARD if poor prognostic factors are present and response is inadequate at 3-6 months.
▸JAK inhibitors carry increased risks of MACE and malignancy compared to TNFi, especially in older patients with cardiovascular risk factors, necessitating careful patient selection.

Rx Drug of Choice: First-line therapy: methotrexate 7.5-25 mg/week orally or subcutaneously plus short-term prednisone (≤10 mg/day tapered over 3-6 months) [125, 357].

Once the acute flare is controlled and organ-threatening disease stabilised, the clinician's focus shifts to achieving sustained remission through a structured, stepwise disease-modifying antirheumatic drug (DMARD) escalation strategy guided by the treat-to-target (T2T) principle ^[359]^A1c. The goal is remission (or at least low disease activity) within 6 months, with monthly assessments and treatment adjustments until the target is reached ^[359]^A1c.

Step 1: First-line Therapy, csDMARD + Short-term Glucocorticoids

Initiate (MTX) as the anchor csDMARD, rapidly escalated to 25 mg/week orally or subcutaneously, combined with a short course of glucocorticoids (GC), e.g., ≤10 mg/day tapered over 3-6 months ^[125]^A1c^[357]^A1c. The EULAR 2022 update recommends MTX plus short-term GC as the initial strategy for all patients with active RA (strong recommendation, moderate-quality evidence) ^[357]^A1c. Methotrexate monotherapy achieves ACR50 response in approximately 41% of MTX-naïve patients, rising to 56-67% when combined with other csDMARDs or biologics ^[477]^A1a. Triple therapy with MTX, sulfasalazine, and hydroxychloroquine is a cost-effective alternative, especially if MTX alone is insufficient ^[477]^A1a.

Step 2: 3-6 Month Assessment, Stratify by Prognostic Factors

Assess disease activity at 3-6 months using a composite measure (e.g., DAS28-CRP, CDAI, SDAI). If the target is not achieved, stratify by the presence of poor prognostic factors (PPF): autoantibodies (RF, ACPA), high disease activity, early erosions, or failure of ≥2 csDMARDs ^[357]^A1c^[462]^A1c.

No PPF: Switch to or add another csDMARD (e.g., leflunomide, sulfasalazine) plus short-term GC ^[357]^A1c.
PPF present: Add a biologic DMARD (bDMARD) or a targeted synthetic DMARD (tsDMARD, i.e., a JAK inhibitor). The 2022 EULAR update recommends adding a bDMARD (any class) after careful consideration of risks; tsDMARDs may be considered after weighing cardiovascular, malignancy, and thromboembolic risks ^[357]^A1c.

Step 3: Add bDMARD or tsDMARD

In patients with PPF, add a bDMARD (TNF inhibitor, abatacept, , , sarilumab) or a JAK inhibitor (tofacitinib, baricitinib, upadacitinib, filgotinib) to background MTX ^[357]^A1c^[462]^A1c. The choice depends on patient preference, comorbidities, cost, and safety profile. Key trials:

Upadacitinib 15 mg once daily + MTX vs placebo: ACR20 at week 12 71% vs 36% (p<0.001), DAS28-CRP <2.6 29% vs 6% ^[338]^A1b. Superior to in ACR50 and DAS28-CRP ≤3.2 at week 12 ^[338]^A1b.
Baricitinib 4 mg once daily + MTX vs placebo: ACR20 at week 12 70% vs 40% (p<0.001), and superior to adalimumab (70% vs 61%, p=0.014) ^[267]^A1b.
Tofacitinib 5 mg twice daily + MTX was non-inferior to adalimumab + MTX (ACR50 at 6 months 46% vs 44%) ^[263]^A1b.
Filgotinib 200 mg once daily + MTX vs placebo: ACR20 at week 12 76.6% vs 49.9% (p<0.001); non-inferior to adalimumab ^[197]^A1b.
Abatacept + MTX vs active conventional therapy in early RA: CDAI remission at 48 weeks 59.3% vs 39.2% (p<0.001) ^[337]^A1b.

Step 4: Failure of First b/tsDMARD, Switch to Another Mechanism

If the first bDMARD or tsDMARD fails (inadequate response or intolerance at 3-6 months), switch to any other bDMARD (from a different or same class) or to a tsDMARD ^[357]^A1c^[125]^A1c. The SELECT-SWITCH trial showed that upadacitinib 15 mg was superior to cycling to a second TNFi (adalimumab) in patients with prior TNFi failure: DAS28-CRP ≤3.2 at week 12 43.3% vs 22.4% (p<0.0001) ^[443]^A1b. In the SELECT-BEYOND trial, upadacitinib demonstrated efficacy in patients with inadequate response to ≥1 bDMARD, with 43% achieving DAS28-CRP ≤3.2 at week 12 ^[344]^A1b.

Step 5: Tapering in Sustained Remission

Once sustained remission (≥6 months) is achieved, DMARDs may be tapered cautiously, but should not be stopped ^[357]^A1c^[125]^A1c. The SORAIRO trial found that in patients in remission, extending the TNF inhibitor interval or reducing MTX dose maintained remission in 76.7% and 79.2% respectively, but in patients with low disease activity, tapering led to loss of control ^[444]^A1b. EULAR recommends tapering bDMARDs by reducing the dose or increasing the interval, while keeping csDMARDs stable ^[357]^A1c.

Drug Comparison Table

Drug class	Starting dose	Key trial	ACR20 response vs placebo	NNT (for ACR50)
MTX (csDMARD)	7.5-25 mg/week	^[477]^A1a	Baseline ~41% (MTX-naïve)	,
Upadacitinib (JAKi)	15 mg once daily	^[338]^A1b	71% vs 36%	5 (95% CI 4-7)
Baricitinib (JAKi)	4 mg once daily	^[267]^A1b	70% vs 40%	5 (95% CI 4-6)
Tofacitinib (JAKi)	5 mg twice daily	^[263]^A1b	51.5% vs 28.3%	6 (95% CI 5-8)
Filgotinib (JAKi)	200 mg once daily	^[197]^A1b	76.6% vs 49.9%	4 (95% CI 3-5)
Abatacept (bDMARD)	125 mg SC weekly	^[337]^A1b	59.3% CDAI remission vs 39.2%	,

NNT calculated from available data; CI from original trials.

Controversies and Guideline Disagreement

Question	Position A	Position B	Strength	Implication
JAK inhibitor safety vs TNFi	EULAR 2022, JAKi may be considered after careful assessment of risks (MACE, malignancy, VTE) ^[357]^A1c	FDA, restricts JAKi use to patients who have failed TNFi, due to ORAL Surveillance results showing increased MACE (HR 1.33, 95% CI 0.91-1.94) and malignancy (HR 1.48, 95% CI 1.04-2.09) with tofacitinib vs TNFi ^[452]^A1b	Strong (different regulatory labels)	JAKi should be reserved for patients without cardiovascular risk factors, age <65, and without history of malignancy; shared decision-making is essential ^[374]^D5.

What NOT to Do

Do not continue DMARDs unchanged beyond 3 months if the target is not met, treat-to-target requires timely escalation ^[359]^A1c.
Do not stop DMARDs completely in sustained remission, flares are common; tapering is preferred ^[357]^A1c^[444]^A1b.
Do not use JAK inhibitors as first-line in patients >65 years with cardiovascular risk factors without careful discussion of risks ^[452]^A1b^[374]^D5.

Pearl: Initiate MTX plus short-term GC in all active RA; escalate to a bDMARD or tsDMARD by 3-6 months if poor prognostic factors are present, and switch to a different mechanism class if the first advanced therapy fails, sustained remission allows cautious tapering but not cessation of all DMARDs ^[357]^A1c^[125]^A1c^[452]^A1b.

csDMARD Dosing and Monitoring

Drug	Starting dose	Target dose	Key monitoring
Methotrexate	7.5-15 mg/week	25 mg/week	LFTs, creatinine, FBC, chest X-ray
Leflunomide	10-20 mg/day	20 mg/day	LFTs, BP, FBC
Sulfasalazine	500 mg twice daily	2-3 g/day	FBC, LFTs, creatinine
Hydroxychloroquine	200-400 mg/day	≤5 mg/kg/day	Retinal screening annually

bDMARD and tsDMARD Dosing and Key Trials

Drug	Dose	Key trial	Primary outcome
Upadacitinib	15 mg once daily	SELECT-NEXT ^[338]^A1b	ACR20 week 12: 71% vs 36%
Baricitinib	4 mg once daily	RA-BEAM ^[267]^A1b	ACR20 week 12: 70% vs 40%
Tofacitinib	5 mg twice daily	ORAL Standard ^[270]^A1b	ACR20 week 6: 51.5% vs 28.3%
Filgotinib	200 mg once daily	FINCH 2 ^[197]^A1b	ACR20 week 12: 76.6% vs 49.9%
Abatacept	125 mg SC weekly	NORD-STAR ^[337]^A1b	CDAI remission week 48: 59.3% vs 39.2%
Rituximab	1000 mg IV days 0 and 14	REFLEX ^[473]^A1a	ACR50 week 24: 29% vs 9%
Tocilizumab	8 mg/kg IV q4w or 162 mg SC weekly	OPTION ^[366]^A1a	ACR50 week 24: 38.8% vs 9.6%

Immunosuppression Safety & Therapeutic Drug Monitoring

▸Proactive therapeutic drug monitoring for infliximab improves sustained disease control without worsening compared to standard therapy (73.6% vs 55.9%, adjusted difference 17.6%) [520].
▸Hydroxychloroquine retinopathy prevalence is higher than previously recognized; annual screening with SD-OCT and visual fields is recommended after 5 years of use [523].
▸Vaccination against influenza, pneumococcus, and herpes zoster (recombinant vaccine) is essential before starting immunosuppression; glucocorticoids carry a dose-dependent infection risk similar to biologics [524].

! Warning: Glucocorticoid use, even at low doses, carries a substantial infection risk that is dose-dependent and comparable to that of biologics [524].

HY High Yield: Proactive TDM for infliximab is supported by a randomized trial showing a 17.6% absolute improvement in sustained disease control; consider implementing in routine practice [520].

Once a treat-to-target strategy is established, the safety of lifelong immunosuppression becomes a parallel priority. Protocolized drug-safety surveillance is a first-class recurring clinical activity in rheumatology, encompassing pre-biologic screening, ongoing laboratory monitoring, retinopathy detection, infection prophylaxis, and perioperative hold rules.

Pre-treatment Screening

Before initiating any biologic or targeted synthetic DMARD (b/tsDMARD), screen for latent tuberculosis (TB) with interferon-gamma release assay or tuberculin skin test, hepatitis B and C serologies, and HIV ^[508]^A1a. In patients with risk factors, check baseline immunoglobulin levels and consider echocardiography for those with heart failure, as TNF inhibitors can exacerbate congestive heart failure ^[522]^D5. For , measure hepatitis B surface antigen and core antibody, and assess immunoglobulin levels; hypogammaglobulinemia increases infection risk ^[510]^A1c.

Laboratory Monitoring

During therapy, monitor , liver enzymes, and serum creatinine every 4-8 weeks initially, then every 3 months. -induced hepatotoxicity is associated with higher erythrocyte methotrexate polyglutamate (MTX-PG) concentrations; the MIRACLE trial showed that total MTX-PG concentration was independently linked to hepatotoxicity, regardless of use ^[504]^A1b. For Janus kinase inhibitors (JAKis), check creatine phosphokinase and lipids at baseline and periodically; upadacitinib and baricitinib are associated with small increases in LDL cholesterol that respond to statin therapy ^[305]^A1b^[507]^B2b. Baricitinib long-term safety data (median 4.6 years, up to 9.3 years) showed no new safety signals, with incidence rates for serious infections of 2.6 per 100 patient-years, 3.0, and major adverse cardiovascular events (MACE) 0.5 ^[507]^B2b. JAKis also increase risk of herpes zoster, particularly in patients aged ≥50 years ^[524]^D5.

Therapeutic Drug Monitoring (TDM)

Proactive TDM during maintenance therapy improves outcomes. In a randomized trial of 458 patients with immune-mediated inflammatory diseases (including RA), proactive TDM with dose and interval adjustments based on serum drug levels and antidrug antibodies resulted in sustained disease control without worsening in 73.6% of patients versus 55.9% with standard therapy (estimated adjusted difference 17.6%, 95% CI 9.0%-26.2%, p<0.001) ^[520]^A1b. TDM is also debated for other biologics, but the 2025 EULAR update recognized TDM as a promising precision-medicine approach ^[509]^A1a.

Infection Prevention

Vaccinate patients against influenza, pneumococcus, and herpes zoster (recombinant zoster vaccine) before starting immunosuppression. Live vaccines are contraindicated during most b/tsDMARD therapy. Glucocorticoids, even at low doses, carry a dose-dependent risk of serious infection similar to that of biologics ^[524]^D5. Nurse-led patient education improves safety skills: the BioSecure score was higher in the intervention group (81.2 vs 75.6, p=0.015) ^[519]^A1b. During the pandemic, glucocorticoid use was associated with increased risk of severe COVID-19, while b/tsDMARD monotherapy (especially anti-TNF) was associated with lower risk ^[511]^B2a.

Retinopathy Screening

Hydroxychloroquine (HCQ) retinopathy was previously underestimated; with modern screening (spectral-domain optical coherence tomography), prevalence is substantially higher than recognized. The major risk factors are cumulative dose >5 g/kg actual body weight, duration >5 years, and renal disease. The American Academy of Ophthalmology recommends baseline and annual screening after 5 years, using automated visual fields and SD-OCT ^[523]^D5.

Perioperative

For elective surgery, hold biologics according to their half-life: TNF inhibitors are typically withheld for 1-2 dosing cycles (e.g., 1 week for , 4 weeks for infliximab) before surgery, and resumed after wound healing (usually 10-14 days). Methotrexate and leflunomide are generally continued, except in cases of high infection risk. Glucocorticoids should be continued at the lowest effective dose to avoid adrenal insufficiency ^[357]^A1c.

Pearl: Proactive TDM for infliximab improves sustained disease control by 17.6% (NNT = 6 to prevent one disease worsening) ^[520]^A1b; always screen for latent TB and hepatitis B before starting any b/tsDMARD, and monitor for herpes zoster when using JAKis.

Recommended Monitoring Schedule for Common DMARDs and Biologics

Drug Class	Pre-treatment Screen	Routine Lab Monitoring	Special Monitoring
Methotrexate	CBC, LFTs, creatinine, hepatitis B/C, CXR	CBC, LFTs, creatinine q4-8w then q3mo	MTX-PG levels if hepatotoxicity suspected ^[504]^A1b
TNF inhibitors (adalimumab, infliximab, etanercept)	TB test (IGRA/TST), hepatitis B/C, HIV	CBC, LFTs, creatinine q3mo	Consider TDM for infliximab ^[520]^A1b
JAK inhibitors (baricitinib, upadacitinib, tofacitinib)	TB test, hepatitis B/C, HIV, CBC, lipids, CPK, LFTs, creatinine	CBC, LFTs, creatinine, lipids, CPK at 1-3mo then q3mo	Herpes zoster risk; check lipids after 12 weeks ^[507]^B2b^[305]^A1b
Rituximab	TB test, hepatitis B/C, HIV, immunoglobulins, CBC, LFTs	CBC, LFTs, creatinine q3mo; immunoglobulins before each cycle	Monitor for hypogammaglobulinemia and late-onset neutropenia ^[510]^A1c
Hydroxychloroquine	None specific	CBC, LFTs, creatinine annually	Annual retinal exam (SD-OCT, visual fields) after 5 years ^[523]^D5

Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)

▸Extra-articular manifestations are common and increase mortality; ILD is the most frequent and serious, with a 20-year cumulative incidence of 15.3%.
▸The 2023 ACR/CHEST guideline recommends screening for ILD with PFTs and HRCT; lung ultrasound and serum biomarkers (KL-6, MMP-7) are emerging adjuncts.
▸Cardiovascular disease remains a leading cause of death; aggressive RA control and traditional risk factor modification are essential.

HY High Yield: Lung cancer risk is increased in RA (aHR 1.58) and especially in RA-ILD (aHR 3.25); maintain a low threshold for chest imaging in smokers [548].

Having navigated the intricacies of immunosuppression safety and therapeutic drug monitoring, the clinician must now turn to the systemic reach of rheumatoid arthritis, which extends well beyond the synovium to involve multiple organs, each with distinct screening, monitoring, and treatment imperatives.

Pulmonary involvement

(ILD) is the most frequent and serious extra-articular manifestation. The 20‑year cumulative incidence of RA-ILD is 15.3% ^[557]^B2b. One‑year mortality in RA-ILD is 13.9% versus 3.8% in RA without ILD, and the hazard ratio for death is 2‑ to 10‑fold higher ^[528]^B2b^[557]^B2b. Key risk factors include older age, male sex, smoking, seropositivity, and the MUC5B promoter variant rs35705950 (OR 3.1 for RA-ILD) ^[562]^B3b^[545]^B2b. Lifetime risk of ILD in MUC5B carriers reaches 16.8% ^[545]^B2b.

The 2023 ACR/CHEST guideline conditionally recommends screening with and high‑resolution CT of the chest ^[127]^A1c. Lung ultrasound shows promising diagnostic accuracy (pooled sensitivity 0.96, specificity 0.97) ^[591]^A1a. Serum biomarkers such as KL‑6 (AUC 0.964) and MMP‑7 also aid detection ^[590]^B3a^[552]^B2b.

Treatment of RA-ILD remains challenging. A network meta-analysis found that , , and were associated with lower all‑cause mortality; abatacept plus methotrexate reduced ILD progression; and antifibrotics (nintedanib, pirfenidone) slowed FVC decline ^[318]^A1a. JAK inhibitors appear to stabilise pulmonary function (FVC change -0.85%, 95% CI -2.40 to 0.71) ^[284]^A1a^[516]^B2b. Baricitinib improved or stabilised FVC in 88% of patients in a real‑world study ^[567]^C4. TNF inhibitors are not systematically contraindicated in RA-ILD ^[531]^B2b but require careful monitoring.

Airway disease also carries excess risk: obstructive lung disease is more common in RA (HR 1.54) ^[560]^B2b, and bronchiectasis contributes to respiratory mortality ^[568]^B2b. Lung cancer risk is elevated (aHR 1.58 overall; aHR 3.25 with RA-ILD) ^[548]^B2b.

Cardiovascular involvement

Cardiovascular disease is a leading cause of death in RA. Pericarditis, , heart failure, and accelerated atherosclerosis all occur ^[230]^D5^[576]^D5. Although coronary heart disease mortality in recent cohorts may not be significantly increased, heart failure risk persists ^[571]^B2b. requires aggressive RA control with DMARDs, plus traditional risk factor modification, , antihypertensives, and smoking cessation ^[576]^D5^[581]^D5.

Ocular involvement

RA is the leading cause of necrotising and peripheral ulcerative (PUK) ^[580]^D5. is more common but less severe. Scleritis and PUK can threaten vision and are associated with systemic vasculitis and excess mortality. Urgent rheumatology and ophthalmology collaboration is essential ^[580]^D5.

Hematologic involvement

Anemia of chronic disease is common and may respond to disease control; erythropoiesis‑stimulating agents have been used but evidence is limited ^[228]^A1a. , neutropenia, splenomegaly, and RA, is a rare but classic triad. Large granular lymphocyte leukaemia may co‑occur.

Cutaneous and other systems

Subcutaneous rheumatoid nodules have declined in incidence (from 30.9% to 15.8% over two decades) ^[529]^B2b but remain a marker of disease severity. Vasculitic ulcers, , and glomerulonephritis are less common but require prompt recognition. Renal involvement is rare and usually due to AA amyloidosis or drug toxicity.

Pearl: The MUC5B promoter variant identifies a subset of RA patients with a 16.8% lifetime risk of ILD; combine clinical risk factors (age, smoking, seropositivity) with baseline PFTs and HRCT to detect ILD before irreversible lung function loss ^[545]^B2b.

Organ System Screening and Management Summary

Organ System	Key Manifestation	Screening/Monitoring	Organ-Specific Management
Pulmonary	ILD, COPD, bronchiectasis	PFTs, HRCT (ACR/CHEST 2023) ^[127]^A1c; LUS emerging	DMARDs + antifibrotics if progressive ^[318]^A1a
Cardiovascular	Heart failure, IHD, pericarditis	BP, lipids, ECG; consider echo	Statins, antihypertensives, DMARDs ^[576]^D5
Ocular	Scleritis, PUK	Ophthalmology referral	Systemic immunosuppression; urgent if PUK ^[580]^D5
Hematologic	Anemia, Felty syndrome	CBC, differential	Treat RA; ESAs for anemia ^[228]^A1a

Complications: Disease-Driven & Treatment-Related

▸RA independently increases MI risk ~1.8-fold and serious infection risk in proportion to disease activity.
▸JAK inhibitors carry increased risks of herpes zoster, malignancy (vs TNFi), and MACE in patients with CV risk factors; absolute excess is low in standard-risk populations.
▸Glucocorticoids cause dose-dependent harm even at 5 mg/day; tapering should be attempted once low disease activity is achieved.

! Warning: Do not use JAK inhibitors in patients aged ≥65 years with cardiovascular risk factors if alternative therapy is available (FDA black box warning based on ORAL Surveillance) [452]. Avoid combining high-dose glucocorticoids (>10 mg/day prednisone equivalent) with biologic DMARDs without rigorous infection monitoring [623].

Beyond the organ-by-organ map of extra-articular disease, the clinician must distinguish damage caused by the disease itself from iatrogenic harm, both dominate long-term morbidity.

Disease-Driven Complications

Cardiovascular disease is the leading cause of death. RA confers an ~1.8-fold increased risk of myocardial infarction independent of traditional risk factors ^[495]^B2b; Mendelian randomization supports causality, with CRP-mediated pathways ^[134]^B2b. Systemic inflammation drives accelerated atherosclerosis through shared IL-1, IL-6, and TNF pathways ^[109]^D5. showed MACE risk comparable to (HR 1.05, 95% CI 0.77-1.43) ^[445]^A1b. However, RA is not a cardiovascular risk-equivalent to diabetes mellitus; absolute MI rates are lower (5.7 vs 10.7 per 1000 person-years) ^[611]^B2b.

Infection risk rises with disease activity. Compared with remission, moderate disease activity increases hospitalized infection risk (HR 1.83) ^[610]^B2b. RA-associated (RA-ILD) further amplifies serious infection risk (sdHR 1.60, 95%), particularly pulmonary infections ^[597]^B3b. RA-ILD itself carries high mortality (HR 1.97, 95% CI 1.43-2.70), with respiratory and infection-related deaths predominating ^[568]^B2b. Abatacept may lower mortality compared with in RA-ILD (95% CI 0.58-0.82) ^[547]^B2b.

Malignancy risk is site-specific. RA is associated with thyroid cancer (HR 1.28) ^[182]^A1a and lymphoproliferative disorders, often linked to Epstein-Barr virus and immunosuppression ^[608]^C4.

Osteoporosis results from both inflammation and glucocorticoid use. Glucocorticoid-induced bone loss occurs early and is dose-dependent; bisphosphonates and teriparatide are effective ^[376]^D5. osteopathy, though rare, presents with tibial or foot fractures and resolves with drug discontinuation (healing in 91% who stop vs 29% who continue) ^[161]^B2b.

Treatment-Related Complications

Infections are the most common serious adverse events. Standard-dose biologics increase serious infection risk versus csDMARDs (OR 1.31, 95% CrI 1.09-1.58) ^[604]^A1a. Tofacitinib carries higher risk than etanercept (aHR 1.41) ^[145]^B3b. JAK inhibitors consistently increase (aHR 3.66 vs csDMARDs) ^[451]^B2a. Glucocorticoids show a dose-dependent effect: even 5 mg/day increases harm (RR 1.24, 95% CL 1.04) ^[378]^A1b; doses >7.5 mg/day raise infection risk substantially ^[524]^D5. Methotrexate increases respiratory infections (RR 1.11, 95% CI 1.02-1.21) and pneumonitis (RR 7.81) ^[196]^A1a.

Malignancy with JAK inhibitors is a key concern. ORAL Surveillance found higher cancer risk with tofacitinib versus TNFi (HR 1.48, 95% CI 1.04-2.09) ^[452]^A1b. Meta-analyses confirm increased malignancy across IMIDs (IRR 1.50, 95% CI 1.16-1.94 vs TNFi) ^[132]^A1a, though absolute excess is negligible in standard-risk populations (~1 per 27,000 person-years) but meaningful in higher-risk patients (~1 per 147 person-years) ^[180]^A1a. Abatacept shows conflicting data: RCTs show no increase versus placebo/TNFi, but observational studies suggest higher malignancy versus other b/tsDMARDs (IRR 1.21, 95% CI 1.15-1.28) ^[151]^B2a. In patients with prior cancer, targeted therapies do not increase recurrence risk overall (HR 0.90, 95% CI 0.74-1.10) ^[594]^B2a, though skin cancer recurrence may be elevated (RR 1.32, 95% CI 1.02-1.72) ^[600]^B2a.

Cardiovascular events with JAK inhibitors: tofacitinib showed MACE HR 1.33 (95% CI 0.91-1.94) versus TNFi ^[452]^A1b; upadacitinib rates were comparable to across CV risk groups ^[131]^B2b. NSAIDs: celecoxib was noninferior to naproxen or ibuprofen for cardiovascular safety (HR 0.93 vs naproxen) ^[453]^A1b.

Glucocorticoid toxicity follows dose-related patterns: cushingoid features, ecchymosis, and sleep disturbance rise linearly; cataract occurs even at <5 mg/day; glaucoma and show thresholds >7.5 mg/day ^[211]^B3b. The GLORIA trial confirmed that 5 mg prednisolone for 2 years increases mostly non-severe adverse events (RR 1.24) ^[378]^A1b. Tapering glucocorticoids (SEMIRA) led to loss of disease control (DAS28-ESR difference 0.61 favouring continuation) ^[390]^A1b.

Other complications: HBV reactivation is low in resolved infection (1.6%) but reaches 14.6% in chronic HBV without prophylaxis ^[601]^B2a. vaccines remain effective, though RA patients have higher breakthrough infection rates than the general population (HR 1.10) ^[163]^B2b. Rituximab impairs humoral and CD8+ T-cell responses to SARS-CoV-2 ^[630]^C4.

Controversies and Guideline Disagreement

Question	Position A	Position B	Strength	Implication
JAKi malignancy risk vs TNFi	ORAL Surveillance and meta-analyses show increased risk (HR 1.48, IRR 1.50) ^[452]^A1b^[132]^A1a	Absolute risk is low in standard-risk populations; benefit-risk may still favour JAKi in selected patients ^[180]^A1a	Strong (regulatory warnings issued)	Avoid JAKi in patients ≥65 with CV risk factors; discuss risk with all patients
Abatacept and malignancy	RCT data show no increase vs placebo/TNFi ^[151]^B2a	Observational data show higher malignancy vs other b/tsDMARDs (IRR 1.21) ^[151]^B2a	Moderate (conflicting evidence sources)	Continue standard monitoring; no change in prescribing without further data
RA as CV risk-equivalent to diabetes	Some guidelines suggest aggressive statin use	Cohort data show RA MI rates lower than diabetes (5.7 vs 10.7 per 1000 PY) ^[611]^B2b	Moderate (risk stratification differs)	Use RA-specific risk calculators; do not automatically treat as diabetes equivalent

Pearl: Uncontrolled disease activity is the strongest driver of both cardiovascular events and serious infections; achieving remission with the safest effective regimen reduces overall complication burden more than avoiding any single drug class.

Key Complications by Drug Class

Drug Class	Key Complications	Evidence
csDMARDs (MTX)	Respiratory infections, pneumonitis (RR 7.81), osteopathy	^[196]^A1a, ^[161]^B2b
TNF inhibitors	Serious infections (OR 1.31), TB reactivation	^[604]^A1a, ^[615]^A1a
JAK inhibitors	Herpes zoster (aHR 3.66), MACE (HR 1.33), malignancy (HR 1.48)	^[451]^B2a, ^[452]^A1b
Tocilizumab	Increased lipids, MACE comparable to etanercept (HR 1.05)	^[445]^A1b, ^[366]^A1a
Abatacept	Malignancy (observational IRR 1.21 vs other b/tsDMARDs)	^[151]^B2a
Rituximab	Infusion reactions, hypogammaglobulinemia, impaired vaccine response	^[612]^D5, ^[630]^C4
Glucocorticoids	Dose-dependent infection, osteoporosis, cataract, diabetes	^[211]^B3b, ^[378]^A1b, ^[524]^D5

History and Evolution of Treatment

▸The treat-to-target paradigm, with methotrexate as anchor and early addition of b/tsDMARDs in poor prognosis patients, is the cornerstone of modern RA management.
▸ORAL Surveillance revealed increased MACE and cancer risk with tofacitinib versus TNFi, leading to FDA black box warnings for all JAK inhibitors.
▸Prevention trials (APIPPRA, ARIAA) demonstrate that abatacept can delay or prevent progression to RA in at-risk individuals.

HY High Yield: ORAL Surveillance: tofacitinib vs TNFi in patients ≥50 years with CV risk factors, MACE HR 1.33 (NNH 111), cancer HR 1.48 (NNH 77) [452].

Methotrexate, introduced in the 1980s, remains the anchor drug in RA , but the therapeutic landscape has been reshaped by biologic and targeted synthetic DMARDs that emerged from an evolving understanding of synovial inflammation ^[100]^D5.

Pre-biologic Era

Before the 1990s, treatment relied on NSAIDs, glucocorticoids, and conventional DMARDs such as gold, penicillamine, sulfasalazine, and hydroxychloroquine. These agents provided symptomatic relief but had limited disease-modifying capacity and significant toxicity. emerged as the most effective conventional synthetic DMARD, with a Cochrane review demonstrating a threefold increase in ACR50 response versus placebo (RR 3.0, 95% CI 1.5-6.0) ^[310]^A1a. Folic acid supplementation (5 mg weekly) reduced hepatotoxicity and intolerance without compromising efficacy ^[658]^D5. Contrary to historical concerns, long-term methotrexate hepatotoxicity is now understood to be largely driven by underlying non-alcoholic fatty liver disease rather than the drug itself ^[110]^D5.

Biologic Revolution

The first TNF inhibitor, , was approved in 1998, followed by and . Combination with methotrexate proved superior to monotherapy ^[100]^D5. The NORD-STAR trial in early RA showed that and , but not , achieved significantly higher CDAI remission rates at 48 weeks compared with active conventional therapy (59.3% and 52.3% vs 39.2%) ^[337]^A1b. The R4RA trial demonstrated that synovial B-cell status did not predict differential response to versus tocilizumab in anti-TNF inadequate responders ^[10]^A1b. The STRAP trial stratified by synovial B-cell signature and found no difference in ACR20 response between etanercept/tocilizumab grouped versus rituximab in B-cell-poor patients ^[8]^A1b.

JAK Inhibitors

, the first JAK inhibitor, was approved in 2012. ORAL Strategy showed tofacitinib plus methotrexate was non-inferior to adalimumab plus methotrexate (ACR50 46% vs 44%) ^[263]^A1b. 4 mg daily demonstrated superiority to adalimumab in RA-BEAM (ACR20 70% vs 61%; NNT 11) ^[267]^A1b. 15 mg daily showed superiority to adalimumab in SELECT-COMPARE, with 5-year data showing sustained CDAI remission (24.6% vs 18.7% by NRI; NNT 17) ^[279]^A1b. 200 mg was non-inferior to adalimumab in FINCH 1 ^[197]^A1b. , an IL-6 inhibitor, was non-inferior to adalimumab ^[269]^A1b. , a PD-1 agonist, showed efficacy in a phase 2a trial ^[268]^A1b.

Safety Concerns

ORAL Surveillance, a mandatory post-marketing safety trial, compared tofacitinib 5 mg and 10 mg twice daily versus TNF inhibitor in patients aged ≥50 years with at least one cardiovascular risk factor. Over a median 4 years, tofacitinib failed to meet non-inferiority for MACE (HR 1.33, 95% CI 0.91-1.94) and cancer (HR 1.48, 95% CI 1.04-2.09) ^[452]^A1b. The absolute risk increase was 0.9% for MACE (NNH 111) and 1.3% for cancer (NNH 77). This led to FDA black box warnings for all JAK inhibitors. Post hoc analysis showed the highest MACE risk in patients with prior atherosclerotic cardiovascular disease (HR 1.98) ^[129]^B2b. Subsequent analyses of upadacitinib in SELECT-COMPARE showed comparable MACE and VTE rates to adalimumab, though and NMSC were higher ^[148]^B2b. The EULAR task force recommends JAK inhibitors only in patients without major cardiovascular risk factors or malignancy ^[125]^A1c.

Treat-to-Target and Guidelines

The treat-to-target paradigm, endorsed by EULAR and ACR, mandates regular disease activity assessment and treatment escalation until remission or low disease activity is achieved ^[125]^A1c. Initial therapy is methotrexate plus short-term glucocorticoids. In patients with poor prognostic factors (autoantibodies, high disease activity, early erosions), any bDMARD or JAK inhibitor should be added if the target is not reached within 3-6 months ^[125]^A1c. On sustained remission, DMARDs may be tapered but not stopped ^[125]^A1c. The ACR 2021 guideline includes 44 recommendations, with strong recommendations for methotrexate monotherapy in early RA and for TNFi or other bDMARDs in patients with inadequate response to methotrexate ^[637]^A1c.

Prevention

The APIPPRA trial showed that 12 months of abatacept reduced progression to RA in at-risk individuals (6% vs 29% during treatment; NNT 4.3) ^[265]^A1b. The ARIAA trial confirmed that 6 months of abatacept reduced MRI inflammation and progression to RA (HR 0.14) ^[262]^A1b. The TREAT EARLIER trial found that methotrexate did not prevent arthritis development but improved symptoms and physical function ^[12]^A1b.

Non-pharmacologic

The ACR strongly recommends consistent engagement in exercise ^[441]^A1c. The Plants for Joints trial showed a multidisciplinary lifestyle program reduced DAS28 by 0.9 points versus usual care ^[353]^A1b.

Pearl: The evolution from NSAIDs to targeted therapies has transformed RA outcomes, but the ORAL Surveillance trial underscores that JAK inhibitors carry a dose-dependent risk of MACE and cancer in older patients with cardiovascular risk factors, mandating careful patient selection and shared decision-making ^[452]^A1b.

Special Populations, Pregnancy & Fertility

▸Treat-to-target preconception care reduces time to pregnancy; avoid MTX, leflunomide, and NSAIDs.
▸Biologic DMARDs (certolizumab, etanercept) can be continued during pregnancy; HCQ and sulfasalazine are safe throughout.
▸Elderly patients require lower MTX starting doses and careful monitoring for toxicity, especially with diuretics.

HY High Yield: Stop methotrexate at least 3 months before conception and wash out leflunomide with cholestyramine (8 g three times daily for 11 days).

! Warning: In patients >70 years, the combination of MTX, diuretics, and proton pump inhibitors markedly increases risk of life-threatening MTX toxicity [717].

The prognosis of RA has improved dramatically with treat-to-target strategies, but these gains are not uniformly distributed across all populations. Specific modifications are required for pregnancy, pediatrics, and the elderly, where standard DMARD pathways carry unique risks.

Pregnancy, Fertility, and Lactation

Women with RA have a prolonged time to pregnancy; 42% take >12 months ^[691]^B2b. High disease activity, NSAID use, and >7.5 mg daily independently delay conception ^[691]^B2b. A treat-to-target approach that avoids NSAIDs and high-dose prednisone reduced median time to pregnancy from 251 days to 91 days ^[704]^B2b. Preconception counseling is mandatory, stop (MTX) 3 months before conception, wash out leflunomide with cholestyramine, and continue hydroxychloroquine (HCQ) and sulfasalazine ^[464]^D5^[706]^D5. HCQ first-trimester exposure is not associated with major congenital malformations (adjusted RR 1.30, 95% CI 0.76-2.23) ^[683]^B2b.

During pregnancy, disease activity often improves but flares postpartum ^[432]^D5^[689]^B2b. Biologic DMARDs, particularly certolizumab pegol and , can be continued, they are associated with lower DAS28-CRP in the second and third trimesters without increased serious infections in offspring (OR 1.4, 95% CI 0.7-2.8) ^[678]^B2b^[686]^B2b. Glucocorticoids should be used at the lowest effective dose; doses ≥10 mg/day increase preterm birth risk (aOR 4.91, 95% CI 1.30-10.59) ^[718]^B2b. RA pregnancies still carry higher risks of preterm birth (OR 1.84), low birth weight (OR 1.65), and small-for-gestational-age infants ^[142]^B2a^[714]^B2b. Active disease amplifies these risks ^[714]^B2b. Lactation is compatible with HCQ, sulfasalazine, prednisone, and TNF inhibitors at standard doses ^[706]^D5.

Pediatrics (Juvenile Idiopathic Arthritis)

Juvenile idiopathic arthritis (JIA) is managed with the same csDMARDs and bDMARDs as RA, but doses are weight- or body-surface-area-based. 24 mg/m² (max 40 mg) subcutaneously every other week, with or without MTX, achieved ACR Pedi 30 response in (no MTX) and 94% (with MTX) at week 16 ^[454]^B2b. Flare rates were significantly lower with adalimumab versus placebo ^[454]^B2b. Extrapolation from adult RA trials accelerates pediatric approval, but long-term safety monitoring remains essential ^[676]^D5.

Elderly-Onset Rheumatoid Arthritis

Patients with elderly-onset RA (EORA, onset ≥60 years) have more comorbidities and erosions at diagnosis but respond well to treat-to-target strategies ^[371]^B2b^[170]^A1b. Biologic use is lower than in younger patients, yet outcomes are similar ^[170]^A1b. IL-6 inhibitors ( ) and JAK inhibitors show better drug retention than TNF inhibitors in EORA ^[684]^B2b. However, MTX toxicity is a critical concern: patients >70 years on diuretics have a significantly higher risk of severe MTX toxicity ^[717]^B3b; consider starting at 7.5-10 mg weekly with careful monitoring of renal function. Filgotinib can be initiated at 100 mg daily in elderly patients ^[713]^D5. Cardiovascular risk is often undertreated, statin and antihypertensive use is lower in EORA despite higher MACE risk ^[716]^B2b.

Immunocompromised Patients

RA patients with additional immunosuppression (e.g., HIV, transplant, chronic infection) require individualized DMARD selection. Perioperatively, the 2022 ACR/AAHKS guideline recommends continuing csDMARDs through surgery, withholding bDMARDs/tsDMARDs for one dosing cycle before elective arthroplasty, and restarting after wound healing ^[674]^A1c. TNF inhibitor use near surgery is associated with a 2.5-fold increased risk of surgical site infection (OR 2.47, 95% CI 1.66-3.68) ^[682]^A1a. Live vaccines are contraindicated during biologic therapy.

Pearl: Elderly patients require lower MTX starting doses and careful monitoring for toxicity, especially with diuretics.

Prevention, Screening & Surveillance

▸Annual CVD risk assessment with SCORE ×1.5 is recommended by EULAR; RA patients have a 1.8-fold increased MI risk.
▸ACR/CHEST 2023 conditionally recommends screening for ILD with PFTs and HRCT in at-risk RA patients.
▸Vaccination coverage remains suboptimal (<50% for influenza and <40% for pneumococcal); a 1-month delay in methotrexate after PCV13 improves immunogenicity.

HY High Yield: The SCORE multiplier of 1.5 for RA patients is a key EULAR recommendation; use it to avoid underestimating CVD risk [126].

Prevention in RA extends across three domains: averting disease onset in at-risk individuals, screening for common comorbidities, and optimizing vaccination and bone health. Pharmacologic primary prevention remains investigational. In ACPA-positive individuals with arthralgia, abatacept 125 mg weekly for 12 months reduced progression to clinical arthritis, 92·8% versus 69·2% remained arthritis-free at 12 months (NNT not calculable from reported data) ^[265]^A1b. However, hydroxychloroquine did not prevent RA in ACPA-positive individuals ^[130]^A1b, and showed no benefit in ACPA-negative arthralgia ^[386]^A1b. Current guidelines recommend against pharmacologic prevention outside clinical trials ^[336]^A1c.

Cardiovascular Risk Screening

EULAR recommends annual CVD risk assessment using the SCORE calculator multiplied by 1.5 in RA patients ^[126]^A1c. RA confers a 1.8-fold increased risk for myocardial infarction ^[495]^B2b and a pooled RR of 1.69 (95% CI 1.50-1.90) ^[721]^B2a. Mendelian randomization supports a causal role for IL-6 signaling ^[277]^B2b. Despite this, screening for lipids and glucose is lower in RA patients without other risk factors ^[733]^B2b.

Screening

The 2023 ACR/CHEST guideline conditionally recommends screening with and high-resolution CT chest in at-risk patients (older age, male sex, smoking, high disease activity) ^[127]^A1c^[526]^A1c. HRCT detects preclinical parenchymal lung disease in 45% of RA patients without known lung disease ^[572]^B2b. Thoracic ultrasound may serve as an adjunct but does not replace HRCT ^[591]^A1a.

Osteoporosis Screening

Baseline bone mineral density is recommended for all RA patients starting glucocorticoids, with repeat testing annually if therapy continues. Zoledronic acid 5 mg IV once yearly was superior to risedronate 5 mg daily for preventing glucocorticoid-induced bone loss (lumbar spine BMD increase 4.06% vs 2.71% in the treatment subgroup) ^[391]^A1b.

Vaccination

Influenza and pneumococcal vaccines are strongly recommended. A 1-month delay in methotrexate initiation after PCV13 improves humoral immunogenicity ^[342]^A1b. The recombinant zoster vaccine (two doses 4 weeks to 6 months apart) is safe in RA patients ≥50 years, with vaccine effectiveness of 60.7% against and 88.7% against ^[399]^B3b. vaccination reduces but does not eliminate severe infection risk (HR 1.29 for hospitalization after vaccination) ^[163]^B2b. Despite guidelines, vaccine coverage is only 50% for influenza and 37% for pneumococcal ^[181]^A1a.

Patient Education

Smoking cessation is paramount: smoking interacts with genetic risk (HR 4.52 for seropositive RA with family history) ^[649]^B2b. Regular physical activity improves quality of life and function ^[723]^A1a. Adherence to the EAT-Lancet diet may reduce RA risk ^[725]^B2b.

Pearl: The most impactful preventive intervention in RA is annual CVD risk assessment using the SCORE multiplier (×1.5) and aggressive of traditional risk factors, as this comorbidity accounts for the majority of excess mortality.

References

[1]
Reinisch W, Hellstrom W, Dolhain RJEM et al.. “Effects of filgotinib on semen parameters and sex hormones in male patients with inflammatory diseases: results from the phase 2, randomised, double-blind, placebo-controlled MANTA and MANTA-RAy studies.” Annals of the rheumatic diseases (2023). PMID: 37137672 ↗
L1RCTCited in: Definition, Classification & Nomenclature
[2]
de Rotte MC, de Jong PH, den Boer E et al.. “Effect of methotrexate use and erythrocyte methotrexate polyglutamate on glycosylated hemoglobin in rheumatoid arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2014). PMID: 24692301 ↗
L1RCTCited in: Definition, Classification & Nomenclature, Acute Management: Flares & Organ-Threatening Disease
[3]
Xie W, Chen T, Xiao S et al.. “Difficult-to-treat rheumatoid arthritis: systematic review and meta-analysis on global prevalence.” Annals of the rheumatic diseases (2025). PMID: 41188120 ↗
L2SR_OBSCited in: Definition, Classification & Nomenclature, Epidemiology, Etiology & Risk Factors
[4]
Yoshida K, Sung YK, Kavanaugh A et al.. “Biologic discontinuation studies: a systematic review of methods.” Annals of the rheumatic diseases (2013). PMID: 23723316 ↗
L2SR_OBSCited in: Definition, Classification & Nomenclature
[5]
Radner H, Neogi T, Smolen JS et al.. “Performance of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: a systematic literature review.” Annals of the rheumatic diseases (2013). PMID: 23592710 ↗
L2SR_OBSCited in: Definition, Classification & Nomenclature
[6]
Lampa J, Nordström D, van Vollenhoven R et al.. “Certolizumab pegol, abatacept, tocilizumab or active conventional therapy in early rheumatoid arthritis: 48-week patient-reported outcomes from the NORD-STAR trial.” The Lancet. Rheumatology (2026). PMID: 41881637 ↗
L1RCTCited in: Definition, Classification & Nomenclature, Clinical Presentation, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, History and Evolution of Treatment
[7]
Fleischmann RM, Saikali W, Lakhanpal S et al.. “Multiple switching between the biosimilar adalimumab PF-06410293 and reference adalimumab in patients with active rheumatoid arthritis: a phase 3, open-label, randomised, parallel-group study.” The Lancet. Rheumatology (2023). PMID: 38251497 ↗
L1RCTCited in: Definition, Classification & Nomenclature
[8]
Rivellese F, Nerviani A, Giorli G et al.. “Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials.” The Lancet. Rheumatology (2023). PMID: 38251532 ↗
L1RCTCited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[9]
Smolen JS, Pangan AL, Emery P et al.. “Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study.” Lancet (London, England) (2019). PMID: 31130260 ↗
L1RCTCited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[10]
Humby F, Durez P, Buch MH et al.. “Rituximab versus tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis (R4RA): 16-week outcomes of a stratified, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial.” Lancet (London, England) (2021). PMID: 33485455 ↗
L1RCTCited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[11]
Bijlsma JWJ, Welsing PMJ, Woodworth TG et al.. “Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial.” Lancet (London, England) (2016). PMID: 27287832 ↗
L1RCTCited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[12]
Krijbolder DI, Verstappen M, van Dijk BT et al.. “Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): a randomised, double-blind, placebo-controlled, proof-of-concept trial.” Lancet (London, England) (2022). PMID: 35871815 ↗
L1RCTCited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[13]
Liu X, Tedeschi SK, Lu B et al.. “Long-Term Physical Activity and Subsequent Risk for Rheumatoid Arthritis Among Women: A Prospective Cohort Study.” Arthritis & rheumatology (Hoboken, N.J.) (2019). PMID: 30920773 ↗
L2COHORTCited in: Definition, Classification & Nomenclature
[14]
Palmowski Y, Buttgereit T, Dejaco C et al.. “"Official View" on Glucocorticoids in Rheumatoid Arthritis: A Systematic Review of International Guidelines and Consensus Statements.” Arthritis care & research (2017). PMID: 28029750 ↗
L5SR_OBSCited in: Definition, Classification & Nomenclature, Acute Management: Flares & Organ-Threatening Disease
[15]
Arab Alkabeya H, Hughes AM, Adams J. “Factors Associated With Hand and Upper Arm Functional Disability in People With Rheumatoid Arthritis: A Systematic Review.” Arthritis care & research (2019). PMID: 30320976 ↗
L2SR_OBSCited in: Definition, Classification & Nomenclature
[16]
Silva DS, Costa F, Baptista IP et al.. “Evidence-Based Research on Effectiveness of Periodontal Treatment in Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis.” Arthritis care & research (2022). PMID: 33973383 ↗
L2SR_OBSCited in: Definition, Classification & Nomenclature
[17]
Desthieux C, Hermet A, Granger B et al.. “Patient-Physician Discordance in Global Assessment in Rheumatoid Arthritis: A Systematic Literature Review With Meta-Analysis.” Arthritis care & research (2016). PMID: 27059693 ↗
L2SR_OBSCited in: Definition, Classification & Nomenclature
[18]
Barber C, Lacaille D, Fortin PR. “Systematic review of validation studies of the use of administrative data to identify serious infections.” Arthritis care & research (2013). PMID: 23335588 ↗
L2SR_OBSCited in: Definition, Classification & Nomenclature
[19]
Hollick RJ, Macfarlane GJ. “Association of Rural Setting With Poorer Disease Outcomes for Patients With Rheumatic Diseases: Results From a Systematic Review of the Literature.” Arthritis care & research (2021). PMID: 32170834 ↗
L2SR_OBSCited in: Definition, Classification & Nomenclature
[20]
Ulijn E, den Broeder N, Ten Cate D et al.. “Limited Diagnostic and Prognostic Value of Routine Radiographs in Newly Presenting Arthritis Suspected of Rheumatoid Arthritis: A Retrospective Study.” Arthritis care & research (2024). PMID: 37933435 ↗
L3COHORTCited in: Definition, Classification & Nomenclature
[21]
Xie W, Chen T, Chen Y et al.. “Associated lifestyle factors and comorbidities of difficult-to-treat rheumatoid arthritis: a systematic review and meta-analysis.” The Lancet. Rheumatology (2026). PMID: 41999719 ↗
L2SR_OBSCited in: Definition, Classification & Nomenclature, Epidemiology, Etiology & Risk Factors, History and Evolution of Treatment
[22]
Chaplin H, Carpenter L, Raz A et al.. “Summarizing current refractory disease definitions in rheumatoid arthritis and polyarticular juvenile idiopathic arthritis: systematic review.” Rheumatology (Oxford, England) (2021). PMID: 33710321 ↗
L5SR_OBSCited in: Definition, Classification & Nomenclature
[23]
Dey M, Busby A, Elwell H et al.. “The use and context of the term 'multimorbidity' in rheumatoid arthritis: a systematic literature review.” Rheumatology (Oxford, England) (2021). PMID: 33682885 ↗
L5SR_OBSCited in: Definition, Classification & Nomenclature
[24]
Strömbeck B, Petersson IF, Vliet Vlieland TP. “Health care quality indicators on the management of rheumatoid arthritis and osteoarthritis: a literature review.” Rheumatology (Oxford, England) (2012). PMID: 23086518 ↗
L5SR_OBSCited in: Definition, Classification & Nomenclature
[25]
Gupta A, Anis S, de Pablo P. “Imaging tests as predictors of progression to rheumatoid arthritis in clinically suspect arthralgia: a systematic review and meta-analysis.” Rheumatology (Oxford, England) (2025). PMID: 39862402 ↗
L2SR_OBSCited in: Definition, Classification & Nomenclature
[26]
Watanabe R, Ebina K, Gon T et al.. “Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study.” Rheumatology (Oxford, England) (2024). PMID: 38724245 ↗
L2COHORTCited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target
[27]
Paalanen K, Puolakka K, Nikiphorou E et al.. “Is seronegative rheumatoid arthritis true rheumatoid arthritis? A nationwide cohort study.” Rheumatology (Oxford, England) (2021). PMID: 33175968 ↗
L2COHORTCited in: Definition, Classification & Nomenclature
[28]
Dey M, Busby A, Elwell H et al.. “Association between social deprivation and disease activity in rheumatoid arthritis: a systematic literature review.” RMD open (2022). PMID: 35450954 ↗
L2SR_OBSCited in: Definition, Classification & Nomenclature
[29]
Duarte C, Ferreira RJO, Welsing PMJ et al.. “Remission definitions guiding immunosuppressive therapy in rheumatoid arthritis: which is best fitted for the purpose?” RMD open (2024). PMID: 38443090 ↗
L1SR_OBSCited in: Definition, Classification & Nomenclature
[30]
Verstappen M, van Mulligen E, de Jong PHP et al.. “DMARD-free remission as novel treatment target in rheumatoid arthritis: A systematic literature review of achievability and sustainability.” RMD open (2020). PMID: 32393523 ↗
L2SR_OBSCited in: Definition, Classification & Nomenclature, Acute Management: Flares & Organ-Threatening Disease
[31]
Nagy G, Roodenrijs NMT, Welsing PM et al.. “EULAR definition of difficult-to-treat rheumatoid arthritis.” Annals of the rheumatic diseases (2020). PMID: 33004335 ↗
L1OTHERCited in: Definition, Classification & Nomenclature, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target
[32]
Aletaha D, Neogi T, Silman AJ et al.. “2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.” Annals of the rheumatic diseases (2010). PMID: 20699241 ↗
L1OTHERCited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[33]
Wallace ZS, Naden RP, Chari S et al.. “The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease.” Annals of the rheumatic diseases (2019). PMID: 31796497 ↗
L1REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[34]
Deane KD, Holers VM. “Rheumatoid Arthritis Pathogenesis, Prediction, and Prevention: An Emerging Paradigm Shift.” Arthritis & rheumatology (Hoboken, N.J.) (2020). PMID: 32602263 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Pathophysiology & Mechanism, Clinical Presentation, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Prevention, Screening & Surveillance
[35]
Studenic P, Aletaha D, de Wit M et al.. “American College of Rheumatology/EULAR Remission Criteria for Rheumatoid Arthritis: 2022 Revision.” Arthritis & rheumatology (Hoboken, N.J.) (2022). PMID: 36274193 ↗
L1OTHERCited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target
[36]
Adams C, Nair N, Plant D et al.. “Identification of Cell-Specific Differential DNA Methylation Associated With Methotrexate Treatment Response in Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2023). PMID: 36716083 ↗
L2OTHERCited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target
[37]
Baker JF, Reed G, Mikuls TR et al.. “Metabolic Syndrome, Adipokines, and Response to Advanced Therapies in Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2024). PMID: 39420627 ↗
L2OTHERCited in: Definition, Classification & Nomenclature
[38]
Liao KP, Sparks JA, Hejblum BP et al.. “Phenome-Wide Association Study of Autoantibodies to Citrullinated and Noncitrullinated Epitopes in Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2017). PMID: 27792870 ↗
L2OTHERCited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[39]
Bennett JL, Hollingsworth KG, Pratt AG et al.. “Skeletal muscle effects of Janus kinase inhibition in rheumatoid arthritis (RAMUS): a single-arm, experimental medicine study.” The Lancet. Rheumatology (2025). PMID: 41109315 ↗
L4OTHERCited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target
[40]
Di Matteo A, Bathon JM, Emery P. “Rheumatoid arthritis.” Lancet (London, England) (2023). PMID: 38240831 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Pathophysiology & Mechanism, Clinical Presentation, Long-term Management: The DMARD Ladder & Treat-to-Target, Prevention, Screening & Surveillance
[41]
Kermani TA, Warrington KJ. “Polymyalgia rheumatica.” Lancet (London, England) (2012). PMID: 23051717 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Pathophysiology & Mechanism, Clinical Presentation
[42]
Williams MA, Srikesavan C, Heine PJ et al.. “Exercise for rheumatoid arthritis of the hand.” The Cochrane database of systematic reviews (2018). PMID: 30063798 ↗
L1SR_OBSCited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[43]
Nakama GY, Peccin MS, Almeida GJ et al.. “Cemented, cementless or hybrid fixation options in total knee arthroplasty for osteoarthritis and other non-traumatic diseases.” The Cochrane database of systematic reviews (2012). PMID: 23076921 ↗
L1SR_OBSCited in: Definition, Classification & Nomenclature
[44]
Towheed TE, Hochberg MC, Shea BJ et al.. “WITHDRAWN: Analgesia and non-aspirin, non-steroidal anti-inflammatory drugs for osteoarthritis of the hip.” The Cochrane database of systematic reviews (2007). PMID: 17636642 ↗
L1SR_OBSCited in: Definition, Classification & Nomenclature, History and Evolution of Treatment, Special Populations, Pregnancy & Fertility
[45]
Kay J, Upchurch KS. “ACR/EULAR 2010 rheumatoid arthritis classification criteria.” Rheumatology (Oxford, England) (2012). PMID: 23221588 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Pathophysiology & Mechanism
[46]
Beydon M, McCoy S, Nguyen Y et al.. “Epidemiology of Sjögren syndrome.” Nature reviews. Rheumatology (2023). PMID: 38110617 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Severity, Disease Activity & Risk Stratification
[47]
Buch MH, Eyre S, McGonagle D. “Persistent inflammatory and non-inflammatory mechanisms in refractory rheumatoid arthritis.” Nature reviews. Rheumatology (2020). PMID: 33293696 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification
[48]
Luppi F, Sebastiani M, Salvarani C et al.. “Acute exacerbation of interstitial lung disease associated with rheumatic disease.” Nature reviews. Rheumatology (2021). PMID: 34876670 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Pathophysiology & Mechanism, Clinical Presentation, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), Complications: Disease-Driven & Treatment-Related
[49]
Bennett JL, Pratt AG, Dodds R et al.. “Rheumatoid sarcopenia: loss of skeletal muscle strength and mass in rheumatoid arthritis.” Nature reviews. Rheumatology (2023). PMID: 36801919 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[50]
Cutolo M, Soldano S, Smith V et al.. “Dynamic macrophage phenotypes in autoimmune and inflammatory rheumatic diseases.” Nature reviews. Rheumatology (2025). PMID: 40721670 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[51]
Holers VM, Demoruelle KM, Buckner JH et al.. “Distinct mucosal endotypes as initiators and drivers of rheumatoid arthritis.” Nature reviews. Rheumatology (2024). PMID: 39251771 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, History and Evolution of Treatment
[52]
Summers GD, Metsios GS, Stavropoulos-Kalinoglou A et al.. “Rheumatoid cachexia and cardiovascular disease.” Nature reviews. Rheumatology (2010). PMID: 20647995 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Severity, Disease Activity & Risk Stratification
[53]
Kwon OC, Lee HS, Yang HJ et al.. “Cognitive impairment risk in patients with rheumatoid arthritis: a population-based cohort study.” RMD open (2026). PMID: 42049395 ↗
L2COHORTCited in: Definition, Classification & Nomenclature
[54]
Ota R, Hirata A, Hata T et al.. “Serious Infection Risk With TNF Inhibitors vs. JAK Inhibitors in Rheumatoid Arthritis: A Nationwide Claims-Based Cohort Study.” Clinical pharmacology and therapeutics (2025). PMID: 41422438 ↗
L2COHORTCited in: Definition, Classification & Nomenclature
[55]
Jang J, Kim WJ, Park SW et al.. “Development of explainable machine learning models to predict side effects in patients with rheumatoid arthritis taking methotrexate treatment: a nationwide multicentre cohort study.” BMJ open (2025). PMID: 41320203 ↗
L2COHORTCited in: Definition, Classification & Nomenclature
[56]
Nagy G, Buch MH. “Strengths and limitations of the EULAR definition for difficult-to-treat rheumatoid arthritis.” RMD open (2025). PMID: 41224490 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature
[57]
Steiner G, Verschueren P, Van Hoovels L et al.. “Classification of rheumatoid arthritis: is it time to revise the criteria?” RMD open (2024). PMID: 38642926 ↗
L5OTHERCited in: Definition, Classification & Nomenclature
[58]
Tan Y, Buch MH. “'Difficult to treat' rheumatoid arthritis: current position and considerations for next steps.” RMD open (2022). PMID: 35896282 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Long-term Management: The DMARD Ladder & Treat-to-Target
[59]
Kronzer VL, Davis JM, Hanson AC et al.. “Association between sinusitis and incident rheumatic diseases: a population-based study.” RMD open (2024). PMID: 38388169 ↗
L3OTHERCited in: Definition, Classification & Nomenclature
[60]
You SH, Minn DK, Cha YJ et al.. “Multimorbidity and risk of infection in patients with rheumatoid arthritis: Population-based case-control study.” Seminars in arthritis and rheumatism (2026). PMID: 41932225 ↗
L3CASE_CONTROLCited in: Definition, Classification & Nomenclature
[61]
Haraguchi A, Kuga T, Kaneda S et al.. “Foot and ankle pain is associated with subsequent daily activity limitation independent of DAS28-CRP in rheumatoid arthritis: a longitudinal cohort study.” Clinical rheumatology (2026). PMID: 42144509 ↗
L2COHORTCited in: Definition, Classification & Nomenclature
[62]
Geenen R, Overman CL, Christensen R et al.. “EULAR recommendations for the health professional's approach to pain management in inflammatory arthritis and osteoarthritis.” Annals of the rheumatic diseases (2018). PMID: 29724726 ↗
L1GUIDELINECited in: Pathophysiology & Mechanism, History and Evolution of Treatment
[63]
Regueiro C, Rodriguez-Rodriguez L, Triguero-Martinez A et al.. “Specific Association of HLA-DRB1*03 With Anti-Carbamylated Protein Antibodies in Patients With Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2019). PMID: 30277011 ↗
L3SR_OBSCited in: Pathophysiology & Mechanism
[64]
Jiang L, Yin J, Ye L et al.. “Novel risk loci for rheumatoid arthritis in Han Chinese and congruence with risk variants in Europeans.” Arthritis & rheumatology (Hoboken, N.J.) (2014). PMID: 24782177 ↗
L3SR_OBSCited in: Pathophysiology & Mechanism
[65]
Wasko MC, Kay J, Hsia EC et al.. “Diabetes mellitus and insulin resistance in patients with rheumatoid arthritis: risk reduction in a chronic inflammatory disease.” Arthritis care & research (2011). PMID: 21452264 ↗
L5SR_OBSCited in: Pathophysiology & Mechanism, History and Evolution of Treatment
[66]
Wu Q, Jiang Y, You C. “The SUMO components in rheumatoid arthritis.” Rheumatology (Oxford, England) (2022). PMID: 35595244 ↗
L5SR_OBSCited in: Pathophysiology & Mechanism
[67]
Qureshi S, Adas M, Cope PJ et al.. “Autoantibodies as predictors of progression to rheumatoid arthritis: a systematic review and meta-analysis.” RMD open (2026). PMID: 41672721 ↗
L2SR_OBSCited in: Pathophysiology & Mechanism, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[68]
Kastrati K, Aletaha D, Burmester GR et al.. “A systematic literature review informing the consensus statement on efficacy and safety of pharmacological treatment with interleukin-6 pathway inhibition with biological DMARDs in immune-mediated inflammatory diseases.” RMD open (2022). PMID: 36260501 ↗
L1SR_OBSCited in: Pathophysiology & Mechanism, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[69]
Xie W, Hou Y, Xiao S et al.. “Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis.” RMD open (2024). PMID: 38413170 ↗
L2SR_OBSCited in: Pathophysiology & Mechanism
[70]
Schett G, Nagy G, Krönke G et al.. “B-cell depletion in autoimmune diseases.” Annals of the rheumatic diseases (2024). PMID: 38777374 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[71]
Bonelli M, Kerschbaumer A, Kastrati K et al.. “Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story.” Annals of the rheumatic diseases (2024). PMID: 37923366 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[72]
McInnes IB, O'Dell JR. “State-of-the-art: rheumatoid arthritis.” Annals of the rheumatic diseases (2010). PMID: 20959326 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[73]
Wu G, Cao B, Zhai H et al.. “EPO promotes the progression of rheumatoid arthritis by inducing desialylation via increasing the expression of neuraminidase 3.” Annals of the rheumatic diseases (2024). PMID: 38272667 ↗
L3OTHERCited in: Pathophysiology & Mechanism
[74]
Okada Y, Eyre S, Suzuki A et al.. “Genetics of rheumatoid arthritis: 2018 status.” Annals of the rheumatic diseases (2018). PMID: 30530827 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[75]
Aletaha D, Kerschbaumer A, Kastrati K et al.. “Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update.” Annals of the rheumatic diseases (2022). PMID: 35953263 ↗
L1OTHERCited in: Pathophysiology & Mechanism
[76]
van den Berg WB, van Lent PL, Joosten LA et al.. “Amplifying elements of arthritis and joint destruction.” Annals of the rheumatic diseases (2007). PMID: 17934095 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[77]
de Vries RR, van der Woude D, Houwing JJ et al.. “Genetics of ACPA-positive rheumatoid arthritis: the beginning of the end?” Annals of the rheumatic diseases (2011). PMID: 21339219 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[78]
Weyand CM, Goronzy JJ. “Immune Aging in Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2025). PMID: 39800938 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Epidemiology, Etiology & Risk Factors
[79]
Najm A, Ferguson LD, McInnes IB. “Cytokine Pathways Driving Diverse Tissue Pathologies in Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2025). PMID: 40922709 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[80]
Falconer J, Murphy AN, Young SP et al.. “Review: Synovial Cell Metabolism and Chronic Inflammation in Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2018). PMID: 29579371 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[81]
Lesturgie-Talarek M, Gonzalez V, Beaudoin L et al.. “Mucosal-Associated Invariant T Cells in Rheumatic Diseases.” Arthritis & rheumatology (Hoboken, N.J.) (2025). PMID: 40395188 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[82]
Kondo Y, Yokosawa M, Kaneko S et al.. “Review: Transcriptional Regulation of CD4+ T Cell Differentiation in Experimentally Induced Arthritis and Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2018). PMID: 29245178 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[83]
Perl A. “Review: Metabolic Control of Immune System Activation in Rheumatic Diseases.” Arthritis & rheumatology (Hoboken, N.J.) (2017). PMID: 28841779 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[84]
Vallerand IA, Lewinson RT, Frolkis AD et al.. “Depression as a risk factor for the development of rheumatoid arthritis: a population-based cohort study.” RMD open (2018). PMID: 30018804 ↗
L2COHORTCited in: Pathophysiology & Mechanism
[85]
Majka DS, Vu TT, Pope RM et al.. “Association of Rheumatoid Factors With Subclinical and Clinical Atherosclerosis in African American Women: The Multiethnic Study of Atherosclerosis.” Arthritis care & research (2017). PMID: 27159164 ↗
L2OTHERCited in: Pathophysiology & Mechanism
[86]
Hum RM, Christofi M, Smith SL et al.. “Synovial immunopathology in psoriatic arthritis: cellular and molecular insights.” The Lancet. Rheumatology (2025). PMID: 41043452 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[87]
Carter LM, Ehrenstein MR, Vital EM. “Evolution and trajectory of B-cell targeted therapies in rheumatic diseases.” The Lancet. Rheumatology (2025). PMID: 40058377 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Clinical Presentation, History and Evolution of Treatment
[88]
Mehta P, Cron RQ, Hartwell J et al.. “Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome.” The Lancet. Rheumatology (2020). PMID: 32373790 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment
[89]
Bugatti S, De Stefano L, Gandolfo S et al.. “Autoantibody-negative rheumatoid arthritis: still a challenge for the rheumatologist.” The Lancet. Rheumatology (2023). PMID: 38251565 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[90]
Hansildaar R, Vedder D, Baniaamam M et al.. “Cardiovascular risk in inflammatory arthritis: rheumatoid arthritis and gout.” The Lancet. Rheumatology (2020). PMID: 32904897 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[91]
Toes RE, Raza K. “The autoimmune response as a potential target for tolerance induction before the development of rheumatoid arthritis.” The Lancet. Rheumatology (2021). PMID: 38279384 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Long-term Management: The DMARD Ladder & Treat-to-Target, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[92]
Schett G, Mackensen A, Mougiakakos D. “CAR T-cell therapy in autoimmune diseases.” Lancet (London, England) (2023). PMID: 37748491 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[93]
McInnes IB, Schett G. “Pathogenetic insights from the treatment of rheumatoid arthritis.” Lancet (London, England) (2017). PMID: 28612747 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[94]
Smolen JS, Aletaha D, Koeller M et al.. “New therapies for treatment of rheumatoid arthritis.” Lancet (London, England) (2007). PMID: 17570481 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[95]
Davies SC, Hussein IM, Nguyen TM et al.. “Oral Janus kinase inhibitors for maintenance of remission in ulcerative colitis.” The Cochrane database of systematic reviews (2020). PMID: 31984480 ↗
L1SR_OBSCited in: Pathophysiology & Mechanism
[96]
Wang B, Lian Y, Gao L et al.. “Global research trends in programmed cell death in rheumatoid arthritis from 2001 to 2025: a bibliometric analysis.” Frontiers in immunology (2026). PMID: 42358954 ↗
L5SR_OBSCited in: Pathophysiology & Mechanism, History and Evolution of Treatment, Prevention, Screening & Surveillance
[97]
Dedmon LE. “The genetics of rheumatoid arthritis.” Rheumatology (Oxford, England) (2020). PMID: 32638005 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Long-term Management: The DMARD Ladder & Treat-to-Target
[98]
González García A, Fernández-Martín J, Robles Marhuenda Á. “Idiopathic multicentric Castleman disease and associated autoimmune and autoinflammatory conditions: practical guidance for diagnosis.” Rheumatology (Oxford, England) (2023). PMID: 35997567 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Clinical Presentation
[99]
Thalhamer T, McGrath MA, Harnett MM. “MAPKs and their relevance to arthritis and inflammation.” Rheumatology (Oxford, England) (2008). PMID: 18187523 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[100]
Upchurch KS, Kay J. “Evolution of treatment for rheumatoid arthritis.” Rheumatology (Oxford, England) (2012). PMID: 23221584 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, History and Evolution of Treatment
[101]
Choy EHS, Calabrese LH. “Neuroendocrine and neurophysiological effects of interleukin 6 in rheumatoid arthritis.” Rheumatology (Oxford, England) (2018). PMID: 29186541 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[102]
Smolen JS. “Poor prognostic factors and unmet needs in rheumatoid arthritis.” Rheumatology (Oxford, England) (2025). PMID: 39798131 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target
[103]
Choy EH. “Clinical significance of Janus Kinase inhibitor selectivity.” Rheumatology (Oxford, England) (2019). PMID: 30508136 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[104]
Orr C, Vieira-Sousa E, Boyle DL et al.. “Synovial tissue research: a state-of-the-art review.” Nature reviews. Rheumatology (2017). PMID: 28701760 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[105]
Nygaard G, Firestein GS. “Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes.” Nature reviews. Rheumatology (2020). PMID: 32393826 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Clinical Presentation
[106]
Zaiss MM, Joyce Wu HJ, Mauro D et al.. “The gut-joint axis in rheumatoid arthritis.” Nature reviews. Rheumatology (2021). PMID: 33674813 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[107]
Szekanecz Z, McInnes IB, Schett G et al.. “Autoinflammation and autoimmunity across rheumatic and musculoskeletal diseases.” Nature reviews. Rheumatology (2021). PMID: 34341562 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[108]
Schrezenmeier E, Dörner T. “Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology.” Nature reviews. Rheumatology (2020). PMID: 32034323 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Complications: Disease-Driven & Treatment-Related
[109]
Weber BN, Giles JT, Liao KP. “Shared inflammatory pathways of rheumatoid arthritis and atherosclerotic cardiovascular disease.” Nature reviews. Rheumatology (2023). PMID: 37231248 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[110]
Di Martino V, Verhoeven DW, Verhoeven F et al.. “Busting the myth of methotrexate chronic hepatotoxicity.” Nature reviews. Rheumatology (2022). PMID: 36564450 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment, Prevention, Screening & Surveillance
[111]
Tanaka Y, Luo Y, O'Shea JJ et al.. “Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach.” Nature reviews. Rheumatology (2022). PMID: 34987201 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[112]
Cutolo M. “Glucocorticoids and chronotherapy in rheumatoid arthritis.” RMD open (2016). PMID: 27042335 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target, Prevention, Screening & Surveillance
[113]
Ye H, Yang Q, Guo H et al.. “Internalisation of neutrophils extracellular traps by macrophages aggravate rheumatoid arthritis via Rab5a.” RMD open (2024). PMID: 38485453 ↗
L5OTHERCited in: Pathophysiology & Mechanism
[114]
Molendijk M, Hazes JM, Lubberts E. “From patients with arthralgia, pre-RA and recently diagnosed RA: what is the current status of understanding RA pathogenesis?” RMD open (2018). PMID: 29480896 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[115]
Błyszczuk P, Szekanecz Z. “Pathogenesis of ischaemic and non-ischaemic heart diseases in rheumatoid arthritis.” RMD open (2020). PMID: 31958278 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[116]
O'Byrne AM, van Baarsen LGM. “Lymph nodes as gatekeepers of autoimmune diseases.” RMD open (2024). PMID: 39658052 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Prevention, Screening & Surveillance
[117]
Dey M, Dey M. “PARP1 as a novel therapeutic and diagnostic tool in autoimmune rheumatic diseases: a systematic literature review.” Rheumatology international (2026). PMID: 42262597 ↗
L5SR_OBSCited in: Pathophysiology & Mechanism
[118]
Qian C, Zhang Z, Wu X et al.. “FGFR1 signaling in rheumatoid arthritis: Mechanisms of bone destruction and therapeutic targeting (Review).” International journal of molecular medicine (2026). PMID: 42429045 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[119]
Xu Z, Liu S, Fu Y et al.. “PRDM1-mediated epigenetic and transcriptional repression mechanisms: a key hub in immune differentiation, tumor progression, and inflammatory responses.” Frontiers in immunology (2026). PMID: 42396452 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[120]
Li Q, Zhang W, Chen Y et al.. “Accelerated immunosenescence in SLE: current evidence and clinical translation.” Frontiers in immunology (2026). PMID: 42389515 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Clinical Presentation
[121]
Chen J, Zhang J, Ma Y et al.. “Paederoside alleviates rheumatoid arthritis by targeting SMAD4 to suppress histone lactylation through inhibiting lactate transport in senescent macrophages.” Phytomedicine : international journal of phytotherapy and phytopharmacology (2026). PMID: 42385428 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[122]
Kurzen N, Weißinger S, Kurzen H. “CURE: a phase-based therapeutic framework for chronic inflammation.” Frontiers in immunology (2026). PMID: 42375359 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[123]
Feng A, Li Q, Jiang N et al.. “The Dual Roles of Regulatory B Cells in Infection, Cancer, and Immunity.” MedComm (2026). PMID: 42368777 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[124]
McDougle DR, Moon JJ, Fox DA. “Myeloid-Derived Suppressor Cells in Inflammatory Arthritis.” International journal of molecular sciences (2026). PMID: 42353085 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
[125]
Smolen JS, Landewé RBM, Bijlsma JWJ et al.. “EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update.” Annals of the rheumatic diseases (2020). PMID: 31969328 ↗
L1GUIDELINECited in: Epidemiology, Etiology & Risk Factors, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[126]
Agca R, Heslinga SC, Rollefstad S et al.. “EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update.” Annals of the rheumatic diseases (2016). PMID: 27697765 ↗
L1GUIDELINECited in: Epidemiology, Etiology & Risk Factors, History and Evolution of Treatment, Prevention, Screening & Surveillance
[127]
Johnson SR, Bernstein EJ, Bolster MB et al.. “2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.” Arthritis & rheumatology (Hoboken, N.J.) (2024). PMID: 38973714 ↗
L1GUIDELINECited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), History and Evolution of Treatment, Prevention, Screening & Surveillance
[128]
Curtis JR, Yamaoka K, Chen YH et al.. “Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial.” Annals of the rheumatic diseases (2022). PMID: 36600185 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[129]
Charles-Schoeman C, Buch MH, Dougados M et al.. “Risk of major adverse cardiovascular events with tofacitinib versus tumour necrosis factor inhibitors in patients with rheumatoid arthritis with or without a history of atherosclerotic cardiovascular disease: a post hoc analysis from ORAL Surveillance.” Annals of the rheumatic diseases (2022). PMID: 36137735 ↗
L2RCTCited in: Epidemiology, Etiology & Risk Factors, History and Evolution of Treatment
[130]
Deane KD, Striebich CC, Feser ML et al.. “A Phase 2 Trial of Hydroxychloroquine in Individuals at Risk for Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2026). PMID: 40884017 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Long-term Management: The DMARD Ladder & Treat-to-Target, Prevention, Screening & Surveillance
[131]
Fleischmann R, Curtis JR, Charles-Schoeman C et al.. “Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme.” Annals of the rheumatic diseases (2023). PMID: 37308218 ↗
L2TRIAL_NONRANDOMCited in: Epidemiology, Etiology & Risk Factors, Complications: Disease-Driven & Treatment-Related
[132]
Russell MD, Stovin C, Alveyn E et al.. “JAK inhibitors and the risk of malignancy: a meta-analysis across disease indications.” Annals of the rheumatic diseases (2023). PMID: 37247942 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related
[133]
Safiri S, Kolahi AA, Hoy D et al.. “Global, regional and national burden of rheumatoid arthritis 1990-2017: a systematic analysis of the Global Burden of Disease study 2017.” Annals of the rheumatic diseases (2019). PMID: 31511227 ↗
L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors
[134]
Yuan S, Carter P, Mason AM et al.. “Genetic Liability to Rheumatoid Arthritis in Relation to Coronary Artery Disease and Stroke Risk.” Arthritis & rheumatology (Hoboken, N.J.) (2022). PMID: 35583917 ↗
L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[135]
Meade T, Joyce C, Perich T et al.. “Prevalence, Severity, and Measures of Anxiety in Rheumatoid Arthritis: A Systematic Review.” Arthritis care & research (2024). PMID: 37779491 ↗
L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Severity, Disease Activity & Risk Stratification
[136]
Pianarosa E, Chomistek K, Hsiao R et al.. “Global Rural and Remote Patients With Rheumatoid Arthritis: A Systematic Review.” Arthritis care & research (2022). PMID: 33181001 ↗
L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Severity, Disease Activity & Risk Stratification
[137]
Meade T, Manolios N, Cumming SR et al.. “Cognitive Impairment in Rheumatoid Arthritis: A Systematic Review.” Arthritis care & research (2018). PMID: 28371512 ↗
L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Severity, Disease Activity & Risk Stratification
[138]
Zhou DJ, Mikuls TR, Schmidt C et al.. “Driving Ability and Safety in Rheumatoid Arthritis: A Systematic Review.” Arthritis care & research (2021). PMID: 31909890 ↗
L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors
[139]
Cho MH, Jung J, Kim TH et al.. “Rheumatoid Arthritis and Risk of Thyroid Cancer: A Nationwide Cohort Study.” Arthritis care & research (2025). PMID: 40511527 ↗
L3COHORTCited in: Epidemiology, Etiology & Risk Factors
[140]
Kunutsor SK, Barrett MC, Beswick AD et al.. “Risk factors for dislocation after primary total hip replacement: a systematic review and meta-analysis of 125 studies involving approximately five million hip replacements.” The Lancet. Rheumatology (2019). PMID: 38229338 ↗
L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors
[141]
Kunutsor SK, Barrett MC, Beswick AD et al.. “Risk factors for dislocation after primary total hip replacement: meta-analysis of 125 studies involving approximately five million hip replacements.” The Lancet. Rheumatology (2019). PMID: 35079707 ↗
L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors
[142]
Singh M, Wambua S, Lee SI et al.. “Autoimmune diseases and adverse pregnancy outcomes: an umbrella review.” Lancet (London, England) (2023). PMID: 37997130 ↗
L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Special Populations, Pregnancy & Fertility, Prevention, Screening & Surveillance
[143]
Singh M, Phillips K, Wang J et al.. “Trends in the prevalence of autoimmune diseases during pregnancy in the UK, 2000-21: a retrospective cohort study.” The Lancet. Rheumatology (2025). PMID: 40473454 ↗
L3COHORTCited in: Epidemiology, Etiology & Risk Factors, Special Populations, Pregnancy & Fertility
[144]
Russell MD, Galloway JB, Andrews CD et al.. “Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.” The Lancet. Rheumatology (2022). PMID: 36447940 ↗
L3COHORTCited in: Epidemiology, Etiology & Risk Factors, Long-term Management: The DMARD Ladder & Treat-to-Target
[145]
Pawar A, Desai RJ, Gautam N et al.. “Risk of admission to hospital for serious infection after initiating tofacitinib versus biologic DMARDs in patients with rheumatoid arthritis: a multidatabase cohort study.” The Lancet. Rheumatology (2020). PMID: 38263664 ↗
L3COHORTCited in: Epidemiology, Etiology & Risk Factors, Complications: Disease-Driven & Treatment-Related
[146]
Conrad N, Misra S, Verbakel JY et al.. “Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK.” Lancet (London, England) (2023). PMID: 37156255 ↗
L2COHORTCited in: Epidemiology, Etiology & Risk Factors
[147]
Smolen JS, Emery P, Rigby W et al.. “Upadacitinib as monotherapy in patients with rheumatoid arthritis and prior inadequate response to methotrexate: results at 260 weeks from the SELECT-MONOTHERAPY randomised study.” RMD open (2025). PMID: 40350200 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[148]
Burmester GR, Mysler E, Taylor P et al.. “Benefit-risk analysis of upadacitinib versus adalimumab in patients with rheumatoid arthritis and higher or lower risk of cardiovascular disease.” RMD open (2025). PMID: 40461266 ↗
L2RCTCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment
[149]
Kragstrup TW, Glintborg B, Svensson AL et al.. “Waiting for JAK inhibitor safety data.” RMD open (2022). PMID: 35197363 ↗
L5RCTCited in: Epidemiology, Etiology & Risk Factors, History and Evolution of Treatment
[150]
Dubovyk V, Vasileiadis GK, Fatima T et al.. “Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: a NORD-STAR study.” RMD open (2024). PMID: 38580350 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors
[151]
Zuckerman BP, Gibson M, Roy R et al.. “Abatacept and the risk of malignancy: a meta-analysis across disease indications.” Rheumatology (Oxford, England) (2025). PMID: 39992258 ↗
L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Complications: Disease-Driven & Treatment-Related
[152]
Matcham F, Rayner L, Steer S et al.. “The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis.” Rheumatology (Oxford, England) (2013). PMID: 24003249 ↗
L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors
[153]
Hiraki LT, Arkema EV, Cui J et al.. “Circulating 25-hydroxyvitamin D level and risk of developing rheumatoid arthritis.” Rheumatology (Oxford, England) (2014). PMID: 25065001 ↗
L3SR_OBSCited in: Epidemiology, Etiology & Risk Factors
[154]
Sandoo A, Veldhuijzen van Zanten JJ, Metsios GS et al.. “Vascular function and morphology in rheumatoid arthritis: a systematic review.” Rheumatology (Oxford, England) (2011). PMID: 21926155 ↗
L5SR_OBSCited in: Epidemiology, Etiology & Risk Factors
[155]
Tanaka Y, Miyazaki Y, Kawanishi M et al.. “Long-term safety and efficacy of anti-TNF multivalent VHH antibodies ozoralizumab in patients with rheumatoid arthritis.” RMD open (2024). PMID: 39179257 ↗
L2TRIAL_NONRANDOMCited in: Epidemiology, Etiology & Risk Factors, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target
[156]
Cîrciumaru A, Kisten Y, Hansson M et al.. “Identification of early risk factors for anti-citrullinated-protein-antibody positive rheumatoid arthritis-a prospective cohort study.” Rheumatology (Oxford, England) (2024). PMID: 38457608 ↗
L2COHORTCited in: Epidemiology, Etiology & Risk Factors, Long-term Management: The DMARD Ladder & Treat-to-Target
[157]
Koduri G, Solomon JJ. “Identification, Monitoring, and Management of Rheumatoid Arthritis-Associated Interstitial Lung Disease.” Arthritis & rheumatology (Hoboken, N.J.) (2023). PMID: 37395725 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), Prevention, Screening & Surveillance
[158]
Safiri S, Kolahi AA, Cross M et al.. “Prevalence, Deaths, and Disability-Adjusted Life Years Due to Musculoskeletal Disorders for 195 Countries and Territories 1990-2017.” Arthritis & rheumatology (Hoboken, N.J.) (2021). PMID: 33150702 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors
[159]
Aymon R, Mongin D, Guemara R et al.. “Incidence of Major Adverse Cardiovascular Events in Patients With Rheumatoid Arthritis Treated With JAK Inhibitors Compared With Biologic Disease-Modifying Antirheumatic Drugs: Data From an International Collaboration of Registries.” Arthritis & rheumatology (Hoboken, N.J.) (2025). PMID: 40230232 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors
[160]
Johnson TM, Frideres H, Roul P et al.. “Performance of the Predicting Risk of Cardiovascular Disease Events Calculator in Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2026). PMID: 41657109 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors
[161]
Robin F, Ghossan R, Mehsen-Cetre N et al.. “METHOFRACT, a methotrexate osteopathy multicentre cohort study.” RMD open (2025). PMID: 40998522 ↗
L2COHORTCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment, Prevention, Screening & Surveillance
[162]
Batko B, Szeląg M, Krajewska-Włodarczyk M et al.. “Comorbidity in incident rheumatoid arthritis: a nationwide case-control study with bidirectional follow-up.” Rheumatology (Oxford, England) (2025). PMID: 39689029 ↗
L3CASE_CONTROLCited in: Epidemiology, Etiology & Risk Factors
[163]
Li H, Wallace ZS, Sparks JA et al.. “Risk of COVID-19 Among Unvaccinated and Vaccinated Patients With Rheumatoid Arthritis: A General Population Study.” Arthritis care & research (2022). PMID: 36161711 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[164]
Kimbrough BA, George RJ, Crowson CS et al.. “Long-Term Outcomes in Seronegative Rheumatoid Arthritis.” Arthritis care & research (2025). PMID: 41386743 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification
[165]
Dawood R, Brubeck HF, Riggles KE et al.. “Exploring Factors Associated With Cognitive Impairment in Rheumatoid Arthritis.” Arthritis care & research (2026). PMID: 41147773 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors
[166]
. “Global, regional, and national burden of rheumatoid arthritis, 1990-2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021.” The Lancet. Rheumatology (2023). PMID: 37795020 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Prevention, Screening & Surveillance
[167]
. “Global, regional, and national burden of other musculoskeletal disorders, 1990-2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021.” The Lancet. Rheumatology (2023). PMID: 37927903 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors
[168]
Smolen JS, Aletaha D, McInnes IB. “Rheumatoid arthritis.” Lancet (London, England) (2016). PMID: 27156434 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target
[169]
Jin Y, Mailloux CM, Gowan K et al.. “NALP1 in vitiligo-associated multiple autoimmune disease.” The New England journal of medicine (2007). PMID: 17377159 ↗
L3OTHERCited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation
[170]
Dag HH, van Onna MGB, Dolhain RJEM et al.. “Treat-to-target strategies are feasible in elderly-onset rheumatoid arthritis given its reassuring risk-benefit profile.” RMD open (2026). PMID: 42399075 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment, Special Populations, Pregnancy & Fertility
[171]
Bassila C, Bassila JC, Slim M. “Efficacy and safety of hydrolyzed collagen supplementation on skin health outcomes: a systematic literature review of randomized controlled trials.” European journal of clinical nutrition (2026). PMID: 42342959 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors
[172]
Geneen LJ, Moore RA, Clarke C et al.. “Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews.” The Cochrane database of systematic reviews (2017). PMID: 28436583 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Complications: Disease-Driven & Treatment-Related
[173]
Geneen LJ, Moore RA, Clarke C et al.. “Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews.” The Cochrane database of systematic reviews (2017). PMID: 28087891 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Complications: Disease-Driven & Treatment-Related
[174]
Garner SE, Fidan D, Frankish RR et al.. “WITHDRAWN: Celecoxib for rheumatoid arthritis.” The Cochrane database of systematic reviews (2017). PMID: 28598564 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, History and Evolution of Treatment
[175]
Fidahic M, Jelicic Kadic A, Radic M et al.. “Celecoxib for rheumatoid arthritis.” The Cochrane database of systematic reviews (2017). PMID: 28597983 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification
[176]
Mudano AS, Tugwell P, Wells GA et al.. “Tai Chi for rheumatoid arthritis.” The Cochrane database of systematic reviews (2019). PMID: 31553478 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Severity, Disease Activity & Risk Stratification
[177]
Mertens M, Singh JA. “Anakinra for rheumatoid arthritis.” The Cochrane database of systematic reviews (2009). PMID: 19160248 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Long-term Management: The DMARD Ladder & Treat-to-Target
[178]
Marks JL, Colebatch AN, Buchbinder R et al.. “Pain management for rheumatoid arthritis and cardiovascular or renal comorbidity.” The Cochrane database of systematic reviews (2011). PMID: 21975789 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors
[179]
Cramp F, Hewlett S, Almeida C et al.. “Non-pharmacological interventions for fatigue in rheumatoid arthritis.” The Cochrane database of systematic reviews (2013). PMID: 23975674 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors
[180]
Gibson M, Allen V, Adas M et al.. “Cancer risk of Janus kinase inhibitors and other advanced therapies in immune-mediated inflammatory diseases: a systematic review and Bayesian network meta-analysis of RCTs.” Annals of the rheumatic diseases (2026). PMID: 42431784 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related
[181]
Du D, Zeng T, Qin J et al.. “Vaccination coverage of influenza and pneumococcal vaccines in patients with rheumatic diseases: a systematic review and meta-analysis.” Rheumatology (Oxford, England) (2026). PMID: 42397204 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Prevention, Screening & Surveillance
[182]
Li X, Liu R, Zhang Y et al.. “Meta-analysis and systematic review: the association between rheumatoid arthritis and the risk of thyroid cancer.” Frontiers in immunology (2026). PMID: 42317320 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Complications: Disease-Driven & Treatment-Related
[183]
Mustafa M. “Sleep-related problems among patients with rheumatoid arthritis in the World Health Organization Eastern Mediterranean region: a systematic review and meta-analysis.” Frontiers in psychiatry (2026). PMID: 42290998 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors
[184]
Hofman ZLM, Roodenrijs NMT, Nikiphorou E et al.. “Difficult-to-treat rheumatoid arthritis: what have we learned and what do we still need to learn?” Rheumatology (Oxford, England) (2025). PMID: 39383505 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, Long-term Management: The DMARD Ladder & Treat-to-Target
[185]
Takanashi S, Takeuchi T, Kaneko Y. “Five-year follow-up of patients with difficult-to-treat rheumatoid arthritis.” Rheumatology (Oxford, England) (2025). PMID: 38851883 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Acute Management: Flares & Organ-Threatening Disease
[186]
Finckh A, Gilbert B, Hodkinson B et al.. “Global epidemiology of rheumatoid arthritis.” Nature reviews. Rheumatology (2022). PMID: 36068354 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, History and Evolution of Treatment, Prevention, Screening & Surveillance
[187]
Karacabeyli D, Lacaille D. “Glucagon-like peptide-1 receptor agonists in arthritis: current insights and future directions.” Nature reviews. Rheumatology (2025). PMID: 41034339 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, Severity, Disease Activity & Risk Stratification
[188]
Nurmohamed MT, Heslinga M, Kitas GD. “Cardiovascular comorbidity in rheumatic diseases.” Nature reviews. Rheumatology (2015). PMID: 26282082 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors
[189]
Hyrich KL, Machado PM. “Rheumatic disease and COVID-19: epidemiology and outcomes.” Nature reviews. Rheumatology (2021). PMID: 33339986 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors
[190]
van Steenbergen HW, Cope AP, van der Helm-van Mil AHM. “Rheumatoid arthritis prevention in arthralgia: fantasy or reality?” Nature reviews. Rheumatology (2023). PMID: 37814057 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, History and Evolution of Treatment
[191]
Bendstrup E, Dieude P, Kreuter M et al.. “Lung disease in rheumatoid arthritis.” Nature reviews. Rheumatology (2026). PMID: 42315602 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[192]
Shinkawa Y, Tanaka M, Nakajima T et al.. “DAS28-ESR may underestimate disease activity in rheumatoid arthritis patients with nonalcoholic fatty liver disease: a retrospective cohort study.” Arthritis research & therapy (2026). PMID: 42421078 ↗
L3COHORTCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification
[193]
Tang K, Zhu L, Shan S et al.. “Global, regional and national trends in the epidemiology of rheumatoid arthritis from 1990 to 2021: an age-period-cohort effect analysis of the global burden of disease study 2021.” RMD open (2025). PMID: 40221149 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors
[194]
Funada M, Miyazaki Y, Nakayamada S et al.. “CT informs detection and treatment options in rheumatoid arthritis complicated by pulmonary non-tuberculous mycobacterial disease from the FIRST registry.” RMD open (2024). PMID: 38866590 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Prevention, Screening & Surveillance
[195]
Zhang XM, Liu L, Yan YD et al.. “Infection risks associated with b/tsDMARDs in rheumatoid arthritis: a systematic review and network meta-analysis.” European journal of clinical pharmacology (2026). PMID: 42426413 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related
[196]
Conway R, Low C, Coughlan RJ et al.. “Methotrexate and lung disease in rheumatoid arthritis: a meta-analysis of randomized controlled trials.” Arthritis & rheumatology (Hoboken, N.J.) (2014). PMID: 24757133 ↗
L1SR_MA_RCTCited in: Clinical Presentation, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), Complications: Disease-Driven & Treatment-Related
[197]
Combe B, Kivitz A, Tanaka Y et al.. “Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial.” Annals of the rheumatic diseases (2021). PMID: 33504485 ↗
L1RCTCited in: Clinical Presentation, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[198]
Fleischmann RM, Genovese MC, Enejosa JV et al.. “Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response.” Annals of the rheumatic diseases (2019). PMID: 31362993 ↗
L1RCTCited in: Clinical Presentation
[199]
Takeuchi T, Kawanishi M, Nakanishi M et al.. “Phase II/III Results of a Trial of Anti-Tumor Necrosis Factor Multivalent NANOBODY Compound Ozoralizumab in Patients With Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2022). PMID: 35729713 ↗
L1RCTCited in: Clinical Presentation, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target
[200]
Burmester GR, Kremer JM, Van den Bosch F et al.. “Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial.” Lancet (London, England) (2018). PMID: 29908669 ↗
L1RCTCited in: Clinical Presentation, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment
[201]
Smolen JS, Kay J, Doyle MK et al.. “Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial.” Lancet (London, England) (2009). PMID: 19560810 ↗
L1RCTCited in: Clinical Presentation
[202]
Aletaha D, Bingham CO, Tanaka Y et al.. “Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy (SIRROUND-T): a randomised, double-blind, placebo-controlled, parallel-group, multinational, phase 3 study.” Lancet (London, England) (2017). PMID: 28215362 ↗
L1RCTCited in: Clinical Presentation
[203]
Smolen JS, Beaulieu A, Rubbert-Roth A et al.. “Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial.” Lancet (London, England) (2008). PMID: 18358926 ↗
L1RCTCited in: Clinical Presentation
[204]
Burmester GR, Blanco R, Charles-Schoeman C et al.. “Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial.” Lancet (London, England) (2013). PMID: 23294500 ↗
L1RCTCited in: Clinical Presentation, Complications: Disease-Driven & Treatment-Related
[205]
Gabay C, Emery P, van Vollenhoven R et al.. “Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial.” Lancet (London, England) (2013). PMID: 23515142 ↗
L1RCTCited in: Clinical Presentation
[206]
Fleischmann R, Kremer J, Cush J et al.. “Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis.” The New England journal of medicine (2012). PMID: 22873530 ↗
L1RCTCited in: Clinical Presentation, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment
[207]
Lee EB, Fleischmann R, Hall S et al.. “Tofacitinib versus methotrexate in rheumatoid arthritis.” The New England journal of medicine (2014). PMID: 24941177 ↗
L1RCTCited in: Clinical Presentation, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[208]
McGagh D, Song K, Yuan H et al.. “Digital health technologies to strengthen patient-centred outcome assessment in clinical trials in inflammatory arthritis.” The Lancet. Rheumatology (2024). PMID: 39089297 ↗
L5TRIAL_NONRANDOMCited in: Clinical Presentation
[209]
Mankia K, Siddle H, Di Matteo A et al.. “A core set of risk factors in individuals at risk of rheumatoid arthritis: a systematic literature review informing the EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis.” RMD open (2021). PMID: 34531306 ↗
L2TRIAL_NONRANDOMCited in: Clinical Presentation
[210]
Motta F, Bizzaro N, Giavarina D et al.. “Rheumatoid factor isotypes in rheumatoid arthritis diagnosis and prognosis: a systematic review and meta-analysis.” RMD open (2023). PMID: 37541740 ↗
L2SR_OBSCited in: Clinical Presentation
[211]
Huscher D, Thiele K, Gromnica-Ihle E et al.. “Dose-related patterns of glucocorticoid-induced side effects.” Annals of the rheumatic diseases (2008). PMID: 18684744 ↗
L3OTHERCited in: Clinical Presentation, Complications: Disease-Driven & Treatment-Related
[212]
Qin Y, Cai ML, Jin HZ et al.. “Age-associated B cells contribute to the pathogenesis of rheumatoid arthritis by inducing activation of fibroblast-like synoviocytes via TNF-α-mediated ERK1/2 and JAK-STAT1 pathways.” Annals of the rheumatic diseases (2022). PMID: 35760450 ↗
L5OTHERCited in: Clinical Presentation
[213]
Wang Y, Xie X, Zhang C et al.. “Rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren's syndrome shared megakaryocyte expansion in peripheral blood.” Annals of the rheumatic diseases (2021). PMID: 34462261 ↗
L3OTHERCited in: Clinical Presentation
[214]
Spagnolo P, Distler O, Ryerson CJ et al.. “Mechanisms of progressive fibrosis in connective tissue disease (CTD)-associated interstitial lung diseases (ILDs).” Annals of the rheumatic diseases (2020). PMID: 33037004 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation
[215]
Tu J, Chen W, Huang W et al.. “Positive feedback loop PU.1-IL9 in Th9 promotes rheumatoid arthritis development.” Annals of the rheumatic diseases (2024). PMID: 39164066 ↗
L5OTHERCited in: Clinical Presentation
[216]
De Giuseppe A, Deichsel A, Reese A et al.. “Collagen-binding integrin α11β1 contributes to joint destruction in arthritic hTNFtg mice.” Annals of the rheumatic diseases (2025). PMID: 40816940 ↗
L5OTHERCited in: Clinical Presentation
[217]
Sendo S, Machado CRL, Boyle DL et al.. “Dysregulated NUB1 and Neddylation Enhances Rheumatoid Arthritis Fibroblast-Like Synoviocyte Inflammatory Responses.” Arthritis & rheumatology (Hoboken, N.J.) (2024). PMID: 38566346 ↗
L5OTHERCited in: Clinical Presentation
[218]
Nakajima S, Tsuchiya H, Ota M et al.. “Synovial Tissue Heterogeneity in Japanese Patients With Rheumatoid Arthritis Elucidated Using a Cell-Type Deconvolution Approach.” Arthritis & rheumatology (Hoboken, N.J.) (2023). PMID: 37390361 ↗
L4OTHERCited in: Clinical Presentation
[219]
Mustelin T, Bottini N, Stanford SM. “The Contribution of PTPN22 to Rheumatic Disease.” Arthritis & rheumatology (Hoboken, N.J.) (2019). PMID: 30507064 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation
[220]
You S, Koh JH, Leng L et al.. “The Tumor-Like Phenotype of Rheumatoid Synovium: Molecular Profiling and Prospects for Precision Medicine.” Arthritis & rheumatology (Hoboken, N.J.) (2018). PMID: 29287304 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation
[221]
Yi K, Jo S, Song W et al.. “Analysis of Single-Cell Transcriptome and Surface Protein Expression in Ankylosing Spondylitis Identifies OX40-Positive and Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Positive Pathogenic Th17 Cells.” Arthritis & rheumatology (Hoboken, N.J.) (2023). PMID: 36787119 ↗
L3OTHERCited in: Clinical Presentation, Acute Management: Flares & Organ-Threatening Disease
[222]
Hadjadj J, Wolfers A, Borisov O et al.. “Clinical manifestations, disease penetrance, and treatment in individuals with SOCS1 insufficiency: a registry-based and population-based study.” The Lancet. Rheumatology (2025). PMID: 40024253 ↗
L2OTHERCited in: Clinical Presentation
[223]
Triaille C, Durez P, Natalucci F et al.. “The relationship between clinical disease activity, synovial inflammatory profile, and treatment response in rheumatoid arthritis.” The Lancet. Rheumatology (2025). PMID: 41106413 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification
[224]
Song K, Satsangi J, Coates LC. “Arthritis complicating inflammatory bowel disease- the future is now.” The Lancet. Rheumatology (2024). PMID: 39032495 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation, Prevention, Screening & Surveillance
[225]
Genovese MC, Gaylis NB, Sikes D et al.. “Safety and efficacy of neurostimulation with a miniaturised vagus nerve stimulation device in patients with multidrug-refractory rheumatoid arthritis: a two-stage multicentre, randomised pilot study.” The Lancet. Rheumatology (2020). PMID: 38273617 ↗
L1OTHERCited in: Clinical Presentation
[226]
Lee YC, Fox RS, Kwakkenbos L et al.. “Pain levels and associated factors in the Scleroderma Patient-centered Intervention Network (SPIN) cohort: a multicentre cross-sectional study.” The Lancet. Rheumatology (2021). PMID: 38287631 ↗
L4OTHERCited in: Clinical Presentation
[227]
Yousry TA, Major EO, Ryschkewitsch C et al.. “Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy.” The New England journal of medicine (2006). PMID: 16510746 ↗
L4OTHERCited in: Clinical Presentation, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[228]
Martí-Carvajal AJ, Agreda-Pérez LH, Solà I et al.. “Erythropoiesis-stimulating agents for anemia in rheumatoid arthritis.” The Cochrane database of systematic reviews (2013). PMID: 23450527 ↗
L1SR_OBSCited in: Clinical Presentation, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[229]
Gómez-Bernal F, Quevedo Abeledo JC, Almeida-Santiago C et al.. “Clinical and serological associations of interferon-α and interferon-γ in rheumatoid arthritis patients.” Rheumatology (Oxford, England) (2026). PMID: 41578968 ↗
L4OTHERCited in: Clinical Presentation
[230]
Voskuyl AE. “The heart and cardiovascular manifestations in rheumatoid arthritis.” Rheumatology (Oxford, England) (2006). PMID: 16980723 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[231]
Colmegna I, Weyand CM. “Haematopoietic stem and progenitor cells in rheumatoid arthritis.” Rheumatology (Oxford, England) (2010). PMID: 20837497 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[232]
Dey M, Nagy G, Nikiphorou E. “Comorbidities and extra-articular manifestations in difficult-to-treat rheumatoid arthritis: different sides of the same coin?” Rheumatology (Oxford, England) (2023). PMID: 36205537 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[233]
Kostine M, Truchetet ME, Schaeverbeke T. “Clinical characteristics of rheumatic syndromes associated with checkpoint inhibitors therapy.” Rheumatology (Oxford, England) (2019). PMID: 31816082 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation
[234]
Cavalli G, Dinarello CA. “Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies.” Rheumatology (Oxford, England) (2015). PMID: 26209330 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation
[235]
Hanlon MM, McGarry T, Marzaioli V et al.. “Rheumatoid arthritis macrophages are primed for inflammation and display bioenergetic and functional alterations.” Rheumatology (Oxford, England) (2023). PMID: 36398893 ↗
L5OTHERCited in: Clinical Presentation
[236]
Zabotti A, Aydin SZ, David P et al.. “Delineating inflammatory from non-inflammatory mechanisms for therapy optimization in psoriatic arthritis.” Nature reviews. Rheumatology (2025). PMID: 40075177 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation
[237]
Udalova IA, Mantovani A, Feldmann M. “Macrophage heterogeneity in the context of rheumatoid arthritis.” Nature reviews. Rheumatology (2016). PMID: 27383913 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation
[238]
Raposo B, Klareskog L, Robinson WH et al.. “The peculiar features, diversity and impact of citrulline-reactive autoantibodies.” Nature reviews. Rheumatology (2024). PMID: 38858604 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[239]
Becker YLC, Duvvuri B, Fortin PR et al.. “The role of mitochondria in rheumatic diseases.” Nature reviews. Rheumatology (2022). PMID: 36175664 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation
[240]
Ulutaş F, Yiğit N, Güngör G et al.. “Inflammatory activity as a predictor of clinical deterioration in interstitial pneumonia with autoimmune features: a comparative cohort study with connective tissue disease-associated interstitial lung disease.” Therapeutic advances in respiratory disease (2026). PMID: 42423229 ↗
L3COHORTCited in: Clinical Presentation, Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[241]
Tison A, Jannat-Khah D, Cappelli LC et al.. “Comparing immune-checkpoint inhibitor-mediated inflammatory arthritis to polymyalgia rheumatica: a prospective cohort study.” Journal for immunotherapy of cancer (2026). PMID: 42208976 ↗
L2COHORTCited in: Clinical Presentation
[242]
Veale DJ, Fearon U. “What makes psoriatic and rheumatoid arthritis so different?” RMD open (2015). PMID: 26509055 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation
[243]
Turcinov S, Sharma RK, De Vries C et al.. “Arthritis progressors have a decreased frequency of circulating autoreactive T cells during the at-risk phase of rheumatoid arthritis.” RMD open (2024). PMID: 39557489 ↗
L2OTHERCited in: Clinical Presentation
[244]
Currado D, Trunfio F, Saracino F et al.. “Patients with psoriatic arthritis and comorbid metabolic syndrome show a difficult-to-treat phenotype: another mosaic tile in the definition of a still undefined subset of patients.” RMD open (2025). PMID: 40545272 ↗
L4OTHERCited in: Clinical Presentation
[245]
Vittecoq O, Brevet P, Gerard B et al.. “On difficulties to define prognostic factors for clinical practice in rheumatoid arthritis.” RMD open (2024). PMID: 39343442 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[246]
Kummer LY, Kuijper LH, Fernández Blanco L et al.. “TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination.” RMD open (2025). PMID: 40759563 ↗
L2OTHERCited in: Clinical Presentation
[247]
Dean NJ, Clifton IJ, Salman R et al.. “Anti-IL-5 biologics and rheumatoid arthritis: a single-centre 500 patient year exposure analysis.” RMD open (2023). PMID: 38114196 ↗
L4OTHERCited in: Clinical Presentation
[248]
Liu R, Xing Q, Liu Z et al.. “Clinical characteristics and treatment of low-dose methotrexate-related adverse reactions in rheumatoid arthritis: a retrospective study.” Naunyn-Schmiedeberg's archives of pharmacology (2026). PMID: 42240664 ↗
L4COHORTCited in: Clinical Presentation
[249]
Ninagawa K, Kudo Y, Kono M et al.. “Adult-Onset LRBA Deficiency Presenting with Rheumatoid Arthritis-Like Manifestations: A Case Report.” Journal of clinical immunology (2026). PMID: 42406167 ↗
L4CASE_REPORTCited in: Clinical Presentation
[250]
Ozduygu G, Kaenmuang P, Guedes ABF et al.. “Systemic Autoimmune Rheumatic Disease-Associated Interstitial Lung Disease: A Pulmonary Perspective on Recent Guidelines.” Advances in therapy (2026). PMID: 42423949 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[251]
Atschekzei F, Dubrowinskaja N, Anim M et al.. “Rare variants in genes related to inborn errors of immunity in patients with rheumatoid arthritis and secondary immunodeficiency.” RMD open (2026). PMID: 42399081 ↗
L4OTHERCited in: Clinical Presentation
[252]
Wang H, Xu J, Li Y et al.. “Prevalence of sarcopenia in patients with rheumatoid arthritis: a cross-sectional study.” RMD open (2026). PMID: 42399074 ↗
L4OTHERCited in: Clinical Presentation
[253]
Nagy G, Roodenrijs NMT, Welsing PMJ et al.. “EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis.” Annals of the rheumatic diseases (2021). PMID: 34407926 ↗
L1GUIDELINECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, History and Evolution of Treatment
[254]
Fraenkel L, Bathon JM, England BR et al.. “2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.” Arthritis care & research (2021). PMID: 34101387 ↗
L1GUIDELINECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, History and Evolution of Treatment
[255]
van Vollenhoven R, Takeuchi T, Pangan AL et al.. “Efficacy and Safety of Upadacitinib Monotherapy in Methotrexate-Naive Patients With Moderately-to-Severely Active Rheumatoid Arthritis (SELECT-EARLY): A Multicenter, Multi-Country, Randomized, Double-Blind, Active Comparator-Controlled Trial.” Arthritis & rheumatology (Hoboken, N.J.) (2020). PMID: 32638504 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[256]
Buttgereit F, Aelion J, Rojkovich B et al.. “Efficacy and Safety of ABBV-3373, a Novel Anti-Tumor Necrosis Factor Glucocorticoid Receptor Modulator Antibody-Drug Conjugate, in Adults with Moderate-to-Severe Rheumatoid Arthritis Despite Methotrexate Therapy: A Randomized, Double-Blind, Active-Controlled Proof-of-Concept Phase IIa Trial.” Arthritis & rheumatology (Hoboken, N.J.) (2023). PMID: 36512671 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment
[257]
Buttgereit F, Singhal A, Kivitz A et al.. “Efficacy and Safety of ABBV-154 for the Treatment of Active Rheumatoid Arthritis: A Phase 2b, Randomized, Placebo-Controlled Trial.” Arthritis & rheumatology (Hoboken, N.J.) (2025). PMID: 40495262 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment
[258]
Kuley R, Duvvuri B, Hasnain S et al.. “Neutrophil Activation Markers and Rheumatoid Arthritis Treatment Response to the JAK1/2 Inhibitor Baricitinib.” Arthritis & rheumatology (Hoboken, N.J.) (2024). PMID: 39431356 ↗
L3RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, History and Evolution of Treatment
[259]
Lange E, Kucharski D, Svedlund S et al.. “Effects of Aerobic and Resistance Exercise in Older Adults With Rheumatoid Arthritis: A Randomized Controlled Trial.” Arthritis care & research (2019). PMID: 29696812 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[260]
Hess A, Tascilar K, Schenker HM et al.. “Disease-associated brain activation predicts clinical response to TNF inhibition in rheumatoid arthritis (PreCePra): a randomised, multicentre, double-blind, placebo-controlled phase 3 study.” The Lancet. Rheumatology (2025). PMID: 40570879 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[261]
Wieczorek M, Kisiel B, Włodarczyk D et al.. “Dual JAK and ROCK inhibition with CPL'116 in patients with rheumatoid arthritis with inadequate response to methotrexate: a randomised, double-blind, placebo-controlled, phase 2 trial.” The Lancet. Rheumatology (2025). PMID: 40516565 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment, Prevention, Screening & Surveillance
[262]
Rech J, Tascilar K, Hagen M et al.. “Abatacept inhibits inflammation and onset of rheumatoid arthritis in individuals at high risk (ARIAA): a randomised, international, multicentre, double-blind, placebo-controlled trial.” Lancet (London, England) (2024). PMID: 38364841 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[263]
Fleischmann R, Mysler E, Hall S et al.. “Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial.” Lancet (London, England) (2017). PMID: 28629665 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[264]
Petri M, Bruce IN, Dörner T et al.. “Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-II).” Lancet (London, England) (2023). PMID: 36848919 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[265]
Cope AP, Jasenecova M, Vasconcelos JC et al.. “Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial.” Lancet (London, England) (2024). PMID: 38364839 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment, Prevention, Screening & Surveillance
[266]
Morand EF, Vital EM, Petri M et al.. “Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-I).” Lancet (London, England) (2023). PMID: 36848918 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[267]
Taylor PC, Keystone EC, van der Heijde D et al.. “Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis.” The New England journal of medicine (2017). PMID: 28199814 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[268]
Tuttle J, Drescher E, Simón-Campos JA et al.. “A Phase 2 Trial of Peresolimab for Adults with Rheumatoid Arthritis.” The New England journal of medicine (2023). PMID: 37195941 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[269]
Smolen JS, Feist E, Fatenejad S et al.. “Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis.” The New England journal of medicine (2022). PMID: 36001712 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[270]
van Vollenhoven RF, Fleischmann R, Cohen S et al.. “Tofacitinib or adalimumab versus placebo in rheumatoid arthritis.” The New England journal of medicine (2012). PMID: 22873531 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target
[271]
O'Dell JR, Mikuls TR, Taylor TH et al.. “Therapies for active rheumatoid arthritis after methotrexate failure.” The New England journal of medicine (2013). PMID: 23755969 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification
[272]
Weinblatt ME, Kavanaugh A, Genovese MC et al.. “An oral spleen tyrosine kinase (Syk) inhibitor for rheumatoid arthritis.” The New England journal of medicine (2010). PMID: 20879879 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Complications: Disease-Driven & Treatment-Related
[273]
McDougall JA, Ferucci ED, Glover J et al.. “Telerheumatology: A Systematic Review.” Arthritis care & research (2017). PMID: 27863164 ↗
L2SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[274]
Suter LG, Fraenkel L, Braithwaite RS. “Role of magnetic resonance imaging in the diagnosis and prognosis of rheumatoid arthritis.” Arthritis care & research (2011). PMID: 21557523 ↗
L2SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[275]
Bredemeier M, de Oliveira FK, Rocha CM. “Low- versus high-dose rituximab for rheumatoid arthritis: a systematic review and meta-analysis.” Arthritis care & research (2014). PMID: 23983134 ↗
L2SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[276]
Rempenault C, Combe B, Barnetche T et al.. “Clinical and Structural Efficacy of Hydroxychloroquine in Rheumatoid Arthritis: A Systematic Review.” Arthritis care & research (2020). PMID: 30629341 ↗
L2SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target
[277]
Swerdlow DI, Holmes MV, Kuchenbaecker KB et al.. “The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis.” Lancet (London, England) (2012). PMID: 22421340 ↗
L2SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Prevention, Screening & Surveillance
[278]
Ton DA, den Hollander NK, van Steenbergen HW et al.. “Comparison of findings on contrast-enhanced MRI of the hand, wrist, and forefoot in healthy controls, two at-risk groups, and patients with rheumatoid arthritis: a cohort study.” The Lancet. Rheumatology (2025). PMID: 40523380 ↗
L2COHORTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[279]
Fleischmann R, Swierkot J, Penn SK et al.. “Long-term safety and efficacy of upadacitinib versus adalimumab in patients with rheumatoid arthritis: 5-year data from the phase 3, randomised SELECT-COMPARE study.” RMD open (2024). PMID: 38806190 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, Immunosuppression Safety & Therapeutic Drug Monitoring, History and Evolution of Treatment
[280]
Taylor PC, Schett G, Huizinga TW et al.. “Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study.” RMD open (2024). PMID: 38942592 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment
[281]
Fleischmann R, Meerwein S, Charles-Schoeman C et al.. “Efficacy and safety of upadacitinib in patients with rheumatoid arthritis and inadequate response or intolerance to biological treatments: results through 5 years from the SELECT-BEYOND study.” RMD open (2024). PMID: 39059811 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[282]
Gehin JE, Klaasen RA, Klami Kristianslund E et al.. “Therapeutic serum level for adalimumab in rheumatoid arthritis: explorative analyses of data from a randomised phase III trial.” RMD open (2024). PMID: 39537558 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, History and Evolution of Treatment
[283]
Kronzer VL, Hayashi K, Yoshida K et al.. “Autoantibodies against citrullinated and native proteins and prediction of rheumatoid arthritis-associated interstitial lung disease: A nested case-control study.” The Lancet. Rheumatology (2023). PMID: 36874209 ↗
L3CASE_CONTROLCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Acute Management: Flares & Organ-Threatening Disease, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[284]
Hilliquin S, Vismara E, Berlengiero V et al.. “Effect of targeted therapies on pulmonary function in rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.” RMD open (2026). PMID: 41856563 ↗
L1SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[285]
van Steenbergen HW, Doornkamp F, Alivernini S et al.. “EULAR/ACR risk stratification criteria for development of rheumatoid arthritis in the risk stage of arthralgia.” Annals of the rheumatic diseases (2025). PMID: 40447498 ↗
L1OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[286]
Li K, Mo W, Wu L et al.. “Novel autoantibodies identified in ACPA-negative rheumatoid arthritis.” Annals of the rheumatic diseases (2021). PMID: 33452006 ↗
L3OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[287]
Buch MH. “Defining refractory rheumatoid arthritis.” Annals of the rheumatic diseases (2018). PMID: 29588276 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[288]
Lee S, Choi E, Chae S et al.. “Identification of MYH9 as a key regulator for synoviocyte migration and invasion through secretome profiling.” Annals of the rheumatic diseases (2023). PMID: 37188496 ↗
L5OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[289]
He Y, Sareila O, Johansson L et al.. “Epitopes targeted by autoantibodies in presymptomatic individuals predict early rheumatoid arthritis.” Annals of the rheumatic diseases (2025). PMID: 40348635 ↗
L2OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[290]
Gessl I, Hana CA, Deimel T et al.. “Tenderness and radiographic progression in rheumatoid arthritis and psoriatic arthritis.” Annals of the rheumatic diseases (2022). PMID: 36261248 ↗
L2OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[291]
Felson D, Lacaille D, LaValley MP et al.. “Re-examining remission definitions in rheumatoid arthritis: considering the 28-Joint Disease Activity Score, C-reactive protein level and patient global assessment.” Annals of the rheumatic diseases (2021). PMID: 34785493 ↗
L5OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[292]
Spiliopoulou A, Colombo M, Plant D et al.. “Association of response to TNF inhibitors in rheumatoid arthritis with quantitative trait loci for CD40 and CD39.” Annals of the rheumatic diseases (2019). PMID: 31036624 ↗
L2OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[293]
Wheeler AM, Baker JF, Riley TR et al.. “Peripheral Biomarker Signatures in Rheumatoid Arthritis-Associated Interstitial Lung Disease.” Arthritis & rheumatology (Hoboken, N.J.) (2025). PMID: 40033001 ↗
L3OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[294]
David P, Di Matteo A, Hen O et al.. “Poly-Refractory Rheumatoid Arthritis: An Uncommon Subset of Difficult to Treat Disease With Distinct Inflammatory and Noninflammatory Phenotypes.” Arthritis & rheumatology (Hoboken, N.J.) (2024). PMID: 38059326 ↗
L4OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[295]
Barry S, Sheng E, Baker JF. “Metabolic Consequences of Rheumatoid Arthritis.” Arthritis care & research (2025). PMID: 40176397 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[296]
Chalupczak NV, Aydemir B, Isaacs A et al.. “Sleep Matters: Exploring the Link Between Sleep Disturbances and Fatigue in Rheumatoid Arthritis.” Arthritis care & research (2025). PMID: 40452358 ↗
L4OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[297]
England BR, Yang Y, Roul P et al.. “Heterogeneity of Rheumatoid Arthritis-Associated Interstitial Lung Disease by Longitudinal Forced Vital Capacity Trajectory and Associations With Disease Outcomes.” Arthritis care & research (2025). PMID: 40771150 ↗
L2OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[298]
Sofíudóttir BK, Harders S, Laursen CB et al.. “Detection of Interstitial Lung Disease in Rheumatoid Arthritis by Thoracic Ultrasound: A Diagnostic Test Accuracy Study.” Arthritis care & research (2024). PMID: 38622106 ↗
L4OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), Prevention, Screening & Surveillance
[299]
Baker JF, Reed G, Poudel DR et al.. “Obesity and Response to Advanced Therapies in Rheumatoid Arthritis.” Arthritis care & research (2022). PMID: 35143117 ↗
L2OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification
[300]
Nettleton E, Carlson K, Putman M. “The emerging risk of overdiagnosis in rheumatoid arthritis and polymyalgia rheumatica.” The Lancet. Rheumatology (2024). PMID: 39341221 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), Prevention, Screening & Surveillance
[301]
Vassilakis KD, Lampadaki K, Nikiphorou E et al.. “Skin cancer in inflammatory arthritis: should we advise screening?” The Lancet. Rheumatology (2025). PMID: 41344357 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[302]
McDermott GC, Gill R, Byrne S et al.. “Risk factors for interstitial lung disease in early rheumatoid arthritis and external validation of screening strategies: a cross-sectional analysis of the prospective SAIL-RA cohort in the USA.” The Lancet. Rheumatology (2025). PMID: 41106411 ↗
L4OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[303]
Orange DE, Yao V, Sawicka K et al.. “RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares.” The New England journal of medicine (2020). PMID: 32668112 ↗
L4OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Acute Management: Flares & Organ-Threatening Disease
[304]
Plenge RM, Seielstad M, Padyukov L et al.. “TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study.” The New England journal of medicine (2007). PMID: 17804836 ↗
L3OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[305]
Fleischmann R, Swierkot J, Durez P et al.. “Long-term safety and efficacy of upadacitinib compared with adalimumab in patients with rheumatoid arthritis: 7-year data from the SELECT-COMPARE study.” RMD open (2026). PMID: 42342288 ↗
L1RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, Immunosuppression Safety & Therapeutic Drug Monitoring, History and Evolution of Treatment
[306]
Meijs AC, Kolmert J, Lindquist S et al.. “First-in-human (phase I) trial of SOL-116, a humanised IgG4 monoclonal antibody targeting bile salt-stimulated lipase, in healthy participants and rheumatoid arthritis patients.” RMD open (2026). PMID: 42331396 ↗
L2RCTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[307]
Williams ACC, Fisher E, Hearn L et al.. “Psychological therapies for the management of chronic pain (excluding headache) in adults.” The Cochrane database of systematic reviews (2020). PMID: 32794606 ↗
L1SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[308]
Rösner S, Englbrecht C, Wehrle R et al.. “Eszopiclone for insomnia.” The Cochrane database of systematic reviews (2018). PMID: 30303519 ↗
L1SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Special Populations, Pregnancy & Fertility
[309]
Maxwell L, Singh JA. “Abatacept for rheumatoid arthritis.” The Cochrane database of systematic reviews (2009). PMID: 19821401 ↗
L1SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification
[310]
Lopez-Olivo MA, Siddhanamatha HR, Shea B et al.. “Methotrexate for treating rheumatoid arthritis.” The Cochrane database of systematic reviews (2014). PMID: 24916606 ↗
L1SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[311]
Robert N, Wong GW, Wright JM. “Effect of cyclosporine on blood pressure.” The Cochrane database of systematic reviews (2010). PMID: 20091657 ↗
L1SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[312]
Kirwan JR, Bijlsma JW, Boers M et al.. “Effects of glucocorticoids on radiological progression in rheumatoid arthritis.” The Cochrane database of systematic reviews (2007). PMID: 17253590 ↗
L1SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Acute Management: Flares & Organ-Threatening Disease, Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[313]
Lenza M, Buchbinder R, Takwoingi Y et al.. “Magnetic resonance imaging, magnetic resonance arthrography and ultrasonography for assessing rotator cuff tears in people with shoulder pain for whom surgery is being considered.” The Cochrane database of systematic reviews (2013). PMID: 24065456 ↗
L2SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[314]
Singh JA, Hossain A, Tanjong Ghogomu E et al.. “Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis.” The Cochrane database of systematic reviews (2017). PMID: 28282491 ↗
L1SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification
[315]
Li G, Tan L, Liu J et al.. “Network meta-analysis of novel diagnostic biomarkers for rheumatoid arthritis: comparative performance of anti-CarP, anti-MCV, and emerging markers.” Frontiers in immunology (2026). PMID: 42382770 ↗
L1SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[316]
van Esveld L, Dikkenberg MVD, Luurssen-Masurel N et al.. “Effects of biologic and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on patient-reported outcome domains in rheumatoid arthritis: a systematic review and network meta-analyses.” RMD open (2026). PMID: 42342282 ↗
L1SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target
[317]
Lage-Hansen PR, Haugegaard T, Sofíudóttir BK et al.. “Understanding patient and physician global assessments in rheumatoid arthritis: A meta-epidemiological study of core outcome set performance.” Seminars in arthritis and rheumatism (2026). PMID: 42330661 ↗
L1SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[318]
Hu Y, Gan Y, Tang M et al.. “Efficacy, safety, and tolerability of treatments for interstitial lung disease associated with rtoid arthritis: A systematic review and network meta-analysis.” Journal of autoimmunity (2026). PMID: 42322667 ↗
L1SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Long-term Management: The DMARD Ladder & Treat-to-Target, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[319]
Yamaoka K, Li Z, Aung KTZM et al.. “2024 Update of the Asia-Pacific League of Associations for Rheumatology (APLAR) Recommendations for Rheumatoid Arthritis Management.” International journal of rheumatic diseases (2026). PMID: 42362943 ↗
L1GUIDELINECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment, Prevention, Screening & Surveillance
[320]
Stavropoulos-Kalinoglou A, Metsios GS, Koutedakis Y et al.. “Obesity in rheumatoid arthritis.” Rheumatology (Oxford, England) (2010). PMID: 20959355 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[321]
Druce KL, Basu N. “Predictors of fatigue in rheumatoid arthritis.” Rheumatology (Oxford, England) (2019). PMID: 31435677 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification
[322]
Sidhu N, Wouters F, Niemantsverdriet E et al.. “MRI-detected synovitis of the small joints predicts rheumatoid arthritis development in large joint undifferentiated inflammatory arthritis.” Rheumatology (Oxford, England) (2022). PMID: 34164662 ↗
L2OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[323]
Fenton SAM, Veldhuijzen van Zanten JJCS, Duda JL et al.. “Sedentary behaviour in rheumatoid arthritis: definition, measurement and implications for health.” Rheumatology (Oxford, England) (2018). PMID: 28398519 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[324]
Leu Agelii M, Sareila O, Lönnblom E et al.. “Autoantibodies to joint-related peptides as predictive markers in early rheumatoid arthritis.” Rheumatology (Oxford, England) (2025). PMID: 39078716 ↗
L2OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[325]
Boeren AMP, Khidir SJH, de Jong PHP et al.. “Patient-reported swelling in arthralgia patients at risk for rheumatoid arthritis: is it of value?” Rheumatology (Oxford, England) (2024). PMID: 37952171 ↗
L2OTHERCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[326]
Konzett V, Aletaha D. “Management strategies in rheumatoid arthritis.” Nature reviews. Rheumatology (2024). PMID: 39448800 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[327]
Robinson WH, Lepus CM, Wang Q et al.. “Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis.” Nature reviews. Rheumatology (2016). PMID: 27539668 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Prevention, Screening & Surveillance
[328]
Kissel T, Toes REM, Huizinga TWJ et al.. “Glycobiology of rheumatic diseases.” Nature reviews. Rheumatology (2022). PMID: 36418483 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria, Severity, Disease Activity & Risk Stratification
[329]
Sellam J, Berenbaum F. “The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.” Nature reviews. Rheumatology (2010). PMID: 20924410 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[330]
Pozsgay J, Szekanecz Z, Sármay G. “Antigen-specific immunotherapies in rheumatic diseases.” Nature reviews. Rheumatology (2017). PMID: 28701761 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[331]
Aletaha D, Blüml S. “Therapeutic implications of autoantibodies in rheumatoid arthritis.” RMD open (2016). PMID: 27252890 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[332]
Hua C, Buttgereit F, Combe B. “Glucocorticoids in rheumatoid arthritis: current status and future studies.” RMD open (2020). PMID: 31958273 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[333]
Dai LY, Ren JQ, Zhao YQ et al.. “The value of arthroscopic synovectomy in the treatment of rheumatoid arthritis: A prospective cohort study.” Clinical rheumatology (2026). PMID: 42366265 ↗
L2COHORTCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[334]
Xu Y, Luo L, Chen Y et al.. “Efficacy and safety of traditional Chinese medicine decoctions as an adjuvant treatment for rheumatoid arthritis: A systematic review and meta-analysis.” Medicine (2026). PMID: 42363544 ↗
L1SR_OBSCited in: Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria
[335]
Smolen JS, Aletaha D, Bijlsma JW et al.. “Treating rheumatoid arthritis to target: recommendations of an international task force.” Annals of the rheumatic diseases (2010). PMID: 20215140 ↗
L1GUIDELINECited in: Severity, Disease Activity & Risk Stratification
[336]
Singh JA, Saag KG, Bridges SL et al.. “2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2015). PMID: 26545940 ↗
L1GUIDELINECited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment, Prevention, Screening & Surveillance
[337]
Østergaard M, van Vollenhoven RF, Rudin A et al.. “Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial.” Annals of the rheumatic diseases (2023). PMID: 37423647 ↗
L1RCTCited in: Severity, Disease Activity & Risk Stratification, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[338]
Fleischmann R, Pangan AL, Song IH et al.. “Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial.” Arthritis & rheumatology (Hoboken, N.J.) (2019). PMID: 31287230 ↗
L1RCTCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[339]
Baker MC, Kavanagh S, Cohen S et al.. “A Randomized, Double-Blind, Sham-Controlled, Clinical Trial of Auricular Vagus Nerve Stimulation for the Treatment of Active Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2023). PMID: 37390360 ↗
L1RCTCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[340]
Santos Moreno P, García Salinas R, Caballero Uribe CV et al.. “Pan American League of Associations for Rheumatology recommendations for the management of rheumatoid arthritis.” The Lancet. Rheumatology (2025). PMID: 41240967 ↗
L1GUIDELINECited in: Severity, Disease Activity & Risk Stratification, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), History and Evolution of Treatment
[341]
Kerschbaumer A, Sepriano A, Bergstra SA et al.. “Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis.” Annals of the rheumatic diseases (2022). PMID: 36368906 ↗
L1SR_OBSCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target
[342]
Morel J, Dernis E, Roux C et al.. “Effect of a 1-month methotrexate delay on pneumococcal vaccine immunogenicity and disease control in patients with early rheumatoid arthritis (VACIMRA): an open-label randomised trial.” The Lancet. Rheumatology (2025). PMID: 40749694 ↗
L1RCTCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment, Prevention, Screening & Surveillance
[343]
Tamai H, Ikeda K, Miyamoto T et al.. “Reduced versus maximum tolerated methotrexate dose concomitant with adalimumab in patients with rheumatoid arthritis (MIRACLE): a randomised, open-label, non-inferiority trial.” The Lancet. Rheumatology (2023). PMID: 38251524 ↗
L1RCTCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[344]
Genovese MC, Fleischmann R, Combe B et al.. “Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial.” Lancet (London, England) (2018). PMID: 29908670 ↗
L1RCTCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment
[345]
Lamb SE, Williamson EM, Heine PJ et al.. “Exercises to improve function of the rheumatoid hand (SARAH): a randomised controlled trial.” Lancet (London, England) (2014). PMID: 25308290 ↗
L1RCTCited in: Severity, Disease Activity & Risk Stratification
[346]
Coates LC, Moverley AR, McParland L et al.. “Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicentre, open-label, randomised controlled trial.” Lancet (London, England) (2015). PMID: 26433318 ↗
L1RCTCited in: Severity, Disease Activity & Risk Stratification
[347]
Rubbert-Roth A, Enejosa J, Pangan AL et al.. “Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis.” The New England journal of medicine (2020). PMID: 33053283 ↗
L1RCTCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[348]
Emery P, Hammoudeh M, FitzGerald O et al.. “Sustained remission with etanercept tapering in early rheumatoid arthritis.” The New England journal of medicine (2014). PMID: 25372086 ↗
L1RCTCited in: Severity, Disease Activity & Risk Stratification
[349]
Genovese MC, Kremer J, Zamani O et al.. “Baricitinib in Patients with Refractory Rheumatoid Arthritis.” The New England journal of medicine (2016). PMID: 27028914 ↗
L1RCTCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[350]
Katchamart W, Johnson S, Lin HJ et al.. “Predictors for remission in rheumatoid arthritis patients: A systematic review.” Arthritis care & research (2010). PMID: 20235210 ↗
L2SR_OBSCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target
[351]
Han L, Hazlewood GS, Barnabe C et al.. “Systematic Review of Outcomes and Patient Experience With Virtual Care in Rheumatoid Arthritis.” Arthritis care & research (2022). PMID: 33650316 ↗
L2SR_OBSCited in: Severity, Disease Activity & Risk Stratification
[352]
Hamann P, Holland R, Hyrich K et al.. “Factors Associated With Sustained Remission in Rheumatoid Arthritis in Patients Treated With Anti-Tumor Necrosis Factor.” Arthritis care & research (2017). PMID: 27564526 ↗
L2SR_OBSCited in: Severity, Disease Activity & Risk Stratification
[353]
Walrabenstein W, Wagenaar CA, van der Leeden M et al.. “A multidisciplinary lifestyle program for rheumatoid arthritis: the 'Plants for Joints' randomized controlled trial.” Rheumatology (Oxford, England) (2023). PMID: 36617162 ↗
L1RCTCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[354]
Silvagni E, Zandonella Callegher S, Mauric E et al.. “Musculoskeletal ultrasound for treating rheumatoid arthritis to target-a systematic literature review.” Rheumatology (Oxford, England) (2022). PMID: 35512175 ↗
L2SR_OBSCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target
[355]
Geenen R, Dures E. “A biopsychosocial network model of fatigue in rheumatoid arthritis: a systematic review.” Rheumatology (Oxford, England) (2019). PMID: 31682275 ↗
L2SR_OBSCited in: Severity, Disease Activity & Risk Stratification
[356]
Gwinnutt JM, Wieczorek M, Rodríguez-Carrio J et al.. “Effects of diet on the outcomes of rheumatic and musculoskeletal diseases (RMDs): systematic review and meta-analyses informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs.” RMD open (2022). PMID: 35654458 ↗
L2SR_OBSCited in: Severity, Disease Activity & Risk Stratification
[357]
Smolen JS, Landewé RBM, Bergstra SA et al.. “EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update.” Annals of the rheumatic diseases (2022). PMID: 36357155 ↗
L1OTHERCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, Immunosuppression Safety & Therapeutic Drug Monitoring
[358]
Smolen JS, Edwards CJ, Konzett V et al.. “EULAR recommendations for the management of rheumatoid arthritis with synthetic and biologic disease-modifying antirheumatic drugs: 2025 update.” Annals of the rheumatic diseases (2026). PMID: 41826212 ↗
L1OTHERCited in: Severity, Disease Activity & Risk Stratification, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target
[359]
Smolen JS, Breedveld FC, Burmester GR et al.. “Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force.” Annals of the rheumatic diseases (2015). PMID: 25969430 ↗
L1REVIEW_NARRATIVECited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target
[360]
Franklyn K, Lau CS, Navarra SV et al.. “Definition and initial validation of a Lupus Low Disease Activity State (LLDAS).” Annals of the rheumatic diseases (2015). PMID: 26458737 ↗
L2OTHERCited in: Severity, Disease Activity & Risk Stratification, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[361]
Meng X, Chen Z, Li T et al.. “Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2023). PMID: 37584284 ↗
L4OTHERCited in: Severity, Disease Activity & Risk Stratification
[362]
Nel HJ, Malmström V, Wraith DC et al.. “Autoantigens in rheumatoid arthritis and the potential for antigen-specific tolerising immunotherapy.” The Lancet. Rheumatology (2020). PMID: 38279365 ↗
L5REVIEW_NARRATIVECited in: Severity, Disease Activity & Risk Stratification, Complications: Disease-Driven & Treatment-Related
[363]
Maassen JM, van Ouwerkerk L, Allaart CF. “Tapering of disease-modifying antirheumatic drugs: an overview for daily practice.” The Lancet. Rheumatology (2021). PMID: 38287612 ↗
L5REVIEW_NARRATIVECited in: Severity, Disease Activity & Risk Stratification
[364]
Alshammari MM, Abood NA, Kahwaji S et al.. “Effectiveness of metformin as an adjunctive therapy in rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials.” BMC rheumatology (2026). PMID: 42351297 ↗
L1SR_MA_RCTCited in: Severity, Disease Activity & Risk Stratification
[365]
Singh JA, Noorbaloochi S, Singh G. “Golimumab for rheumatoid arthritis.” The Cochrane database of systematic reviews (2010). PMID: 20091667 ↗
L1SR_OBSCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target
[366]
Singh JA, Beg S, Lopez-Olivo MA. “Tocilizumab for rheumatoid arthritis.” The Cochrane database of systematic reviews (2010). PMID: 20614469 ↗
L1SR_OBSCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related
[367]
Wilsdon TD, Whittle SL, Thynne TR et al.. “Methotrexate for psoriatic arthritis.” The Cochrane database of systematic reviews (2019). PMID: 30656673 ↗
L1SR_OBSCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target
[368]
Chen J, Veras MM, Liu C et al.. “Methotrexate for ankylosing spondylitis.” The Cochrane database of systematic reviews (2013). PMID: 23450553 ↗
L1SR_OBSCited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target
[369]
Kieffer C, Hebert V, Joly P et al.. “Efficacy and Safety of Rituximab in Pemphigus Foliaceus: A Systematic Review and Meta-analysis.” Dermatology and therapy (2026). PMID: 42390708 ↗
L2SR_OBSCited in: Severity, Disease Activity & Risk Stratification
[370]
Konzett V, Kerschbaumer A, Willmann L et al.. “Detectable safety gestalt of rheumatoid arthritis treatments from pivotal clinical drug trials.” Rheumatology (Oxford, England) (2026). PMID: 42360790 ↗
L1SR_OBSCited in: Severity, Disease Activity & Risk Stratification, History and Evolution of Treatment
[371]
Dag HH, Snoeck Henkemans SVJ, Looijen AEM et al.. “Eye-openers for advanced management of elderly-onset rheumatoid arthritis.” Rheumatology (Oxford, England) (2025). PMID: 40795771 ↗
L2OTHERCited in: Severity, Disease Activity & Risk Stratification, Special Populations, Pregnancy & Fertility
[372]
Taylor PC. “Clinical efficacy of launched JAK inhibitors in rheumatoid arthritis.” Rheumatology (Oxford, England) (2019). PMID: 30806707 ↗
L5REVIEW_NARRATIVECited in: Severity, Disease Activity & Risk Stratification
[373]
Brock J, Basu N, Schlachetzki JCM et al.. “Immune mechanisms of depression in rheumatoid arthritis.” Nature reviews. Rheumatology (2023). PMID: 37923863 ↗
L5REVIEW_NARRATIVECited in: Severity, Disease Activity & Risk Stratification
[374]
Szekanecz Z, Buch MH, Charles-Schoeman C et al.. “Efficacy and safety of JAK inhibitors in rheumatoid arthritis: update for the practising clinician.” Nature reviews. Rheumatology (2024). PMID: 38216757 ↗
L5REVIEW_NARRATIVECited in: Severity, Disease Activity & Risk Stratification, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment, Prevention, Screening & Surveillance
[375]
Kurowska-Stolarska M, Alivernini S. “Synovial tissue macrophages in joint homeostasis, rheumatoid arthritis and disease remission.” Nature reviews. Rheumatology (2022). PMID: 35672464 ↗
L5REVIEW_NARRATIVECited in: Severity, Disease Activity & Risk Stratification
[376]
Briot K, Roux C. “Glucocorticoid-induced osteoporosis.” RMD open (2015). PMID: 26509049 ↗
L5REVIEW_NARRATIVECited in: Severity, Disease Activity & Risk Stratification, Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[377]
Goodman SM, Miller AS, Turgunbaev M et al.. “Clinical Practice Guidelines: Incorporating Input From a Patient Panel.” Arthritis care & research (2017). PMID: 28620968 ↗
L5GUIDELINECited in: Acute Management: Flares & Organ-Threatening Disease, Special Populations, Pregnancy & Fertility
[378]
Boers M, Hartman L, Opris-Belinski D et al.. “Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: the pragmatic randomised, double-blind placebo-controlled GLORIA trial.” Annals of the rheumatic diseases (2022). PMID: 35641125 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment, Prevention, Screening & Surveillance
[379]
Fu Q, Wu C, Dai M et al.. “Leflunomide versus azathioprine for maintenance therapy of lupus nephritis: a prospective, multicentre, randomised trial and long-term follow-up.” Annals of the rheumatic diseases (2022). PMID: 35788493 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[380]
Ruyssen-Witrand A, Brusq C, Masson M et al.. “Comparison of two strategies of glucocorticoid withdrawal in patients with rheumatoid arthritis in low disease activity (STAR): a randomised, placebo- controlled, double-blind trial.” Annals of the rheumatic diseases (2025). PMID: 39874233 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease
[381]
Kjørholt KE, Sundlisæter NP, Aga AB et al.. “Three-Year Results of Tapering Tumor Necrosis Factor Inhibitor to Withdrawal Compared to Stable Tumor Necrosis Factor Inhibitor Among Patients With Rheumatoid Arthritis in Sustained Remission: A Multicenter Randomized Trial.” Arthritis & rheumatology (Hoboken, N.J.) (2025). PMID: 40289847 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease
[382]
Krause D, Mai A, Klaassen-Mielke R et al.. “The Efficacy of Short-Term Bridging Strategies With High- and Low-Dose Prednisolone on Radiographic and Clinical Outcomes in Active Early Rheumatoid Arthritis: A Double-Blind, Randomized, Placebo-Controlled Trial.” Arthritis & rheumatology (Hoboken, N.J.) (2022). PMID: 35643951 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease
[383]
Kedra J, Dieudé P, Giboin C et al.. “Towards the Lowest Efficacious Dose: Results From a Multicenter Noninferiority Randomized Open-Label Controlled Trial Assessing Tocilizumab or Abatacept Injection Spacing in Rheumatoid Arthritis in Remission.” Arthritis & rheumatology (Hoboken, N.J.) (2024). PMID: 37942714 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease
[384]
Kerschbaumer A, Sepriano A, Smolen JS et al.. “Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis.” Annals of the rheumatic diseases (2020). PMID: 32033937 ↗
L1SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target
[385]
van Ouwerkerk L, Verschueren P, Boers M et al.. “Initial glucocorticoid bridging in rheumatoid arthritis: does it affect glucocorticoid use over time?” Annals of the rheumatic diseases (2024). PMID: 37607810 ↗
L1SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease
[386]
Dumoulin QA, Krijbolder DI, Visser K et al.. “Development of rheumatoid arthritis after methotrexate in anticitrullinated protein antibody-negative people with clinically suspect arthralgia at risk of rheumatoid arthritis: 4-year data from the TREAT EARLIER trial.” The Lancet. Rheumatology (2024). PMID: 39303731 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment, Prevention, Screening & Surveillance
[387]
Kjørholt KE, Sundlisæter NP, Aga AB et al.. “Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial.” The Lancet. Rheumatology (2024). PMID: 38583450 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease
[388]
Conaghan PG, Nowak M, Du S et al.. “Evaluation of BMS-986142, a reversible Bruton's tyrosine kinase inhibitor, for the treatment of rheumatoid arthritis: a phase 2, randomised, double-blind, dose-ranging, placebo-controlled, adaptive design study.” The Lancet. Rheumatology (2023). PMID: 38251590 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease
[389]
Skaria TG, Sreeprakash A, Umesh R et al.. “Withholding methotrexate after vaccination with ChAdOx1 nCov19 in patients with rheumatoid or psoriatic arthritis in India (MIVAC I and II): results of two, parallel, assessor-masked, randomised controlled trials.” The Lancet. Rheumatology (2022). PMID: 36320825 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease
[390]
Burmester GR, Buttgereit F, Bernasconi C et al.. “Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial.” Lancet (London, England) (2020). PMID: 32711802 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease, Complications: Disease-Driven & Treatment-Related
[391]
Reid DM, Devogelaer JP, Saag K et al.. “Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial.” Lancet (London, England) (2009). PMID: 19362675 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease, Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[392]
Buttgereit F, Doering G, Schaeffler A et al.. “Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial.” Lancet (London, England) (2008). PMID: 18207016 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease
[393]
Goodman SM, Springer B, Guyatt G et al.. “2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.” Arthritis care & research (2017). PMID: 28620917 ↗
L1SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease, Special Populations, Pregnancy & Fertility
[394]
Buttgereit F, Boyadzhieva Z, Reisch M et al.. “Recommendations of the German, Austrian and Swiss rheumatology and other medical societies for the management of polymyalgia rheumatica.” Rheumatology (Oxford, England) (2026). PMID: 41346249 ↗
L1GUIDELINECited in: Acute Management: Flares & Organ-Threatening Disease, History and Evolution of Treatment
[395]
Stanmore EK, Oldham J, Skelton DA et al.. “Fall incidence and outcomes of falls in a prospective study of adults with rheumatoid arthritis.” Arthritis care & research (2013). PMID: 23139011 ↗
L2COHORTCited in: Acute Management: Flares & Organ-Threatening Disease
[396]
Lane JCE, Weaver J, Kostka K et al.. “Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study.” The Lancet. Rheumatology (2020). PMID: 32864627 ↗
L3COHORTCited in: Acute Management: Flares & Organ-Threatening Disease
[397]
Bertrand D, Joly J, Neerinckx B et al.. “Effectiveness of methotrexate and bridging glucocorticoids with or without early introduction of a 6-month course of etanercept in early RA: results of the 2-year, pragmatic, randomised CareRA2020 trial.” RMD open (2024). PMID: 39117445 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease, History and Evolution of Treatment
[398]
Lend K, Twisk JW, Kumar N et al.. “Glucocorticoid treatment in early rheumatoid arthritis is independently associated with increased PCSK9 levels: data from a randomised controlled trial.” RMD open (2025). PMID: 40480650 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease
[399]
Rayens E, Sy LS, Qian L et al.. “Effectiveness and safety of the recombinant zoster vaccine in individuals ≥50 years of age with rheumatoid arthritis: a matched cohort and self-controlled case series study.” Annals of the rheumatic diseases (2025). PMID: 39979209 ↗
L3CASE_REPORTCited in: Acute Management: Flares & Organ-Threatening Disease, Prevention, Screening & Surveillance
[400]
Bijlsma JW. “Disease control with glucocorticoid therapy in rheumatoid arthritis.” Rheumatology (Oxford, England) (2012). PMID: 22685274 ↗
L1SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease
[401]
Ravindran V, Rachapalli S, Choy EH. “Safety of medium- to long-term glucocorticoid therapy in rheumatoid arthritis: a meta-analysis.” Rheumatology (Oxford, England) (2009). PMID: 19447767 ↗
L1SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease
[402]
Hayashi S, Tachibana S, Maeda T et al.. “Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study.” Rheumatology (Oxford, England) (2024). PMID: 37924201 ↗
L2COHORTCited in: Acute Management: Flares & Organ-Threatening Disease
[403]
Rodríguez-Carrio J, Burska A, Conaghan PG et al.. “Association between type I interferon pathway activation and clinical outcomes in rheumatic and musculoskeletal diseases: a systematic literature review informing EULAR points to consider.” RMD open (2023). PMID: 36882218 ↗
L2SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease
[404]
Coburn BW, Baker JF, Hsu JY et al.. “Association of Cardiovascular Outcomes With Low-Dose Glucocorticoid Prescription in Patients With Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2024). PMID: 38923870 ↗
L2OTHERCited in: Acute Management: Flares & Organ-Threatening Disease
[405]
Prisco L, Moll M, Wang J et al.. “Relationship Between Rheumatoid Arthritis and Pulmonary Function Measures on Spirometry in the UK Biobank.” Arthritis & rheumatology (Hoboken, N.J.) (2021). PMID: 33982900 ↗
L4OTHERCited in: Acute Management: Flares & Organ-Threatening Disease
[406]
Manzo A, Bozzalla Cassione E, Montecucco C et al.. “Prediction of long-term drug-free outcomes in ACPA-positive and ACPA-negative rheumatoid arthritis by combined clinical and ultrasound assessment of residual disease: a 5-year prospective study.” RMD open (2025). PMID: 39880410 ↗
L2COHORTCited in: Acute Management: Flares & Organ-Threatening Disease
[407]
Schmajuk G, Trupin L, Yelin E et al.. “Prevalence of Arthritis and Rheumatoid Arthritis in Coal Mining Counties of the United States.” Arthritis care & research (2019). PMID: 30875457 ↗
L4OTHERCited in: Acute Management: Flares & Organ-Threatening Disease
[408]
Yazdany J, Tonner C, Schmajuk G et al.. “Receipt of glucocorticoid monotherapy among Medicare beneficiaries with rheumatoid arthritis.” Arthritis care & research (2014). PMID: 25244314 ↗
L2OTHERCited in: Acute Management: Flares & Organ-Threatening Disease
[409]
Goodman SM, Mirza SZ, DiCarlo EF et al.. “Rheumatoid Arthritis Flares After Total Hip and Total Knee Arthroplasty: Outcomes at One Year.” Arthritis care & research (2020). PMID: 31609524 ↗
L2OTHERCited in: Acute Management: Flares & Organ-Threatening Disease
[410]
Wilson JC, Sarsour K, Gale S et al.. “Incidence and Risk of Glucocorticoid-Associated Adverse Effects in Patients With Rheumatoid Arthritis.” Arthritis care & research (2019). PMID: 29856128 ↗
L2OTHERCited in: Acute Management: Flares & Organ-Threatening Disease
[411]
George MD, Baker JF, Wallace B et al.. “Variability in Glucocorticoid Prescribing for Rheumatoid Arthritis and the Influence of Provider Preference on Long-Term Use of Glucocorticoids.” Arthritis care & research (2021). PMID: 32702188 ↗
L2OTHERCited in: Acute Management: Flares & Organ-Threatening Disease
[412]
Buttgereit F, Tam LS. “Glucocorticoid treatment in patients with inflammatory rheumatic diseases: current practice and open questions.” The Lancet. Rheumatology (2026). PMID: 41936369 ↗
L5REVIEW_NARRATIVECited in: Acute Management: Flares & Organ-Threatening Disease
[413]
Barnes PJ, Adcock IM. “Glucocorticoid resistance in inflammatory diseases.” Lancet (London, England) (2009). PMID: 19482216 ↗
L5REVIEW_NARRATIVECited in: Acute Management: Flares & Organ-Threatening Disease
[414]
Nevins IS, van der Pol JA, Van Ouwerkerk L et al.. “Induction of Cure in Early Arthritis (I CEA): results of a randomised clinical trial to compare three treatment strategies in recent onset undifferentiated arthritis.” RMD open (2026). PMID: 42209019 ↗
L1RCTCited in: Acute Management: Flares & Organ-Threatening Disease
[415]
Pamuk ON, Harmandar F. “A case of cervical spine meningioma following etanercept use in a patient with RA.” Nature reviews. Rheumatology (2009). PMID: 19648944 ↗
L4CASE_REPORTCited in: Acute Management: Flares & Organ-Threatening Disease
[416]
Wechalekar MD, Vinik O, Schlesinger N et al.. “Intra-articular glucocorticoids for acute gout.” The Cochrane database of systematic reviews (2013). PMID: 23633379 ↗
L1SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease
[417]
Gonçalves-Bradley DC, J Maria AR, Ricci-Cabello I et al.. “Mobile technologies to support healthcare provider to healthcare provider communication and management of care.” The Cochrane database of systematic reviews (2020). PMID: 32813281 ↗
L2SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease, Prevention, Screening & Surveillance
[418]
Verhoef LM, van den Bemt BJ, van der Maas A et al.. “Down-titration and discontinuation strategies of tumour necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity.” The Cochrane database of systematic reviews (2019). PMID: 31125448 ↗
L1SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease
[419]
van Herwaarden N, den Broeder AA, Jacobs W et al.. “Down-titration and discontinuation strategies of tumor necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity.” The Cochrane database of systematic reviews (2014). PMID: 25264908 ↗
L1SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease, History and Evolution of Treatment
[420]
Ponkilainen V, Karjalainen TV, Kuitunen I et al.. “Perioperative use of disease-modifying anti-rheumatic drugs (DMARDs) in people with inflammatory arthritis.” The Cochrane database of systematic reviews (2026). PMID: 42159164 ↗
L1SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease, Special Populations, Pregnancy & Fertility
[421]
Lee YH, Song GG. “Risk of disease flare and clinical reversibility following discontinuation versus dose reduction of biological DMARDs in Rheumatoid arthritis: A systematic review and meta-analysis.” Seminars in arthritis and rheumatism (2026). PMID: 42269230 ↗
L1SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease
[422]
Palmowski A, Haugegaard T, Hafström I et al.. “Changes in bone mineral density and fractures during 2 years of low-dose glucocorticoid treatment for rheumatoid arthritis: a systematic literature review and individual participant data meta-analysis.” RMD open (2026). PMID: 42097691 ↗
L1SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease
[423]
Wallace BI, Moore MN, Heisler AC et al.. “Fibromyalgianess and glucocorticoid persistence among patients with rheumatoid arthritis.” Rheumatology (Oxford, England) (2022). PMID: 34293092 ↗
L2OTHERCited in: Acute Management: Flares & Organ-Threatening Disease
[424]
Keystone EC, Smolen J, van Riel P. “Developing an effective treatment algorithm for rheumatoid arthritis.” Rheumatology (Oxford, England) (2012). PMID: 22718927 ↗
L5REVIEW_NARRATIVECited in: Acute Management: Flares & Organ-Threatening Disease
[425]
Kirwan JR, Buttgereit F. “Symptom control with low-dose glucocorticoid therapy for rheumatoid arthritis.” Rheumatology (Oxford, England) (2012). PMID: 22685271 ↗
L5REVIEW_NARRATIVECited in: Acute Management: Flares & Organ-Threatening Disease
[426]
Buttgereit F, Smolen JS, Coogan AN et al.. “Clocking in: chronobiology in rheumatoid arthritis.” Nature reviews. Rheumatology (2015). PMID: 25800214 ↗
L5REVIEW_NARRATIVECited in: Acute Management: Flares & Organ-Threatening Disease
[427]
Smolen JS, Aletaha D. “Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges.” Nature reviews. Rheumatology (2015). PMID: 25687177 ↗
L5REVIEW_NARRATIVECited in: Acute Management: Flares & Organ-Threatening Disease, Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[428]
Buttgereit F, Palmowski A, Bond M et al.. “Osteoporosis and fracture risk are multifactorial in patients with inflammatory rheumatic diseases.” Nature reviews. Rheumatology (2024). PMID: 38831028 ↗
L5REVIEW_NARRATIVECited in: Acute Management: Flares & Organ-Threatening Disease
[429]
Baschant U, Lane NE, Tuckermann J. “The multiple facets of glucocorticoid action in rheumatoid arthritis.” Nature reviews. Rheumatology (2012). PMID: 23045254 ↗
L5REVIEW_NARRATIVECited in: Acute Management: Flares & Organ-Threatening Disease
[430]
Buttgereit F. “Views on glucocorticoid therapy in rheumatology: the age of convergence.” Nature reviews. Rheumatology (2020). PMID: 32076129 ↗
L5REVIEW_NARRATIVECited in: Acute Management: Flares & Organ-Threatening Disease
[431]
Hoes JN, Jacobs JW, Buttgereit F et al.. “Current view of glucocorticoid co-therapy with DMARDs in rheumatoid arthritis.” Nature reviews. Rheumatology (2010). PMID: 21119718 ↗
L5REVIEW_NARRATIVECited in: Acute Management: Flares & Organ-Threatening Disease
[432]
Förger F, Villiger PM. “Immunological adaptations in pregnancy that modulate rheumatoid arthritis disease activity.” Nature reviews. Rheumatology (2020). PMID: 31932747 ↗
L5REVIEW_NARRATIVECited in: Acute Management: Flares & Organ-Threatening Disease, Special Populations, Pregnancy & Fertility
[433]
Chen AY, Wolchok JD, Bass AR. “TNF in the era of immune checkpoint inhibitors: friend or foe?” Nature reviews. Rheumatology (2021). PMID: 33686279 ↗
L5REVIEW_NARRATIVECited in: Acute Management: Flares & Organ-Threatening Disease
[434]
Pan J, Zhu YY, Zou YW et al.. “Long-term dynamic of muscle mass and its effectors in female patients with rheumatoid arthritis: a 5-year prospective cohort study.” Therapeutic advances in musculoskeletal disease (2026). PMID: 42130900 ↗
L2COHORTCited in: Acute Management: Flares & Organ-Threatening Disease
[435]
Zhang Q, Qi Y, Wang X et al.. “Hospitalization risk in patients with rheumatoid arthritis-associated interstitial lung disease or bronchiectasis: A matched cohort study.” Seminars in arthritis and rheumatism (2026). PMID: 42127546 ↗
L2COHORTCited in: Acute Management: Flares & Organ-Threatening Disease
[436]
Gumber L, Rayner F, Bigirumurame T et al.. “Patient-reported outcomes as early warning signs of flare following drug cessation in rheumatoid arthritis.” RMD open (2025). PMID: 40169281 ↗
L2OTHERCited in: Acute Management: Flares & Organ-Threatening Disease
[437]
Adami G, Fassio A, Rossini M et al.. “Tapering glucocorticoids and risk of flare in rheumatoid arthritis on biological disease-modifying antirheumatic drugs (bDMARDs).” RMD open (2023). PMID: 36599630 ↗
L3OTHERCited in: Acute Management: Flares & Organ-Threatening Disease
[438]
Zhao L, Ma S, Chen S et al.. “The Role of Therapeutic Apheresis in the Management of Rheumatoid Arthritis A Systematic Review and Meta-Analysis.” Journal of clinical apheresis (2026). PMID: 42389975 ↗
L1SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease
[439]
Gao Y, Ye G, Gao L et al.. “Meta-Analysis of the Incidence and Influencing Factors of Malignant Tumors in Patients with Rheumatoid Arthritis.” Journal of epidemiology and global health (2026). PMID: 42185654 ↗
L2SR_OBSCited in: Acute Management: Flares & Organ-Threatening Disease
[440]
Duch KS, Alkattan M, Holm TÁM et al.. “Glucocorticoid use among patients with rheumatoid arthritis during the first year of treatment-a cohort study.” Rheumatology international (2026). PMID: 42283855 ↗
L2COHORTCited in: Acute Management: Flares & Organ-Threatening Disease
[441]
England BR, Smith BJ, Baker NA et al.. “2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2023). PMID: 37227071 ↗
L1GUIDELINECited in: Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[442]
England BR, Smith BJ, Baker NA et al.. “2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis.” Arthritis care & research (2023). PMID: 37227116 ↗
L1GUIDELINECited in: Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[443]
Mysler E, Sidiropoulos PI, Balanescu A et al.. “Upadacitinib vs adalimumab in patients with rheumatoid arthritis and a prior inadequate response or intolerance to a tumour necrosis factor inhibitor: 12-week results from the randomised, double-blind, SELECT-SWITCH study.” Annals of the rheumatic diseases (2026). PMID: 41991443 ↗
L1RCTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[444]
Imai Y, Kono M, Ishii T et al.. “Spacing of a TNF inhibitor or dose reduction of methotrexate vs continued treatment in patients with rheumatoid arthritis in remission or low disease activity: a randomised, controlled trial (SORAIRO trial).” Annals of the rheumatic diseases (2026). PMID: 41763966 ↗
L1RCTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[445]
Giles JT, Sattar N, Gabriel S et al.. “Cardiovascular Safety of Tocilizumab Versus Etanercept in Rheumatoid Arthritis: A Randomized Controlled Trial.” Arthritis & rheumatology (Hoboken, N.J.) (2020). PMID: 31469238 ↗
L1RCTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment
[446]
Winkler A, Sun W, De S et al.. “The Interleukin-1 Receptor-Associated Kinase 4 Inhibitor PF-06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial.” Arthritis & rheumatology (Hoboken, N.J.) (2021). PMID: 34423919 ↗
L1RCTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[447]
Choi MY, Barnabe C, Barber CE et al.. “Pragmaticism of Randomized Controlled Trials of Biologic Treatment With Methotrexate in Rheumatoid Arthritis: A Systematic Review.” Arthritis care & research (2019). PMID: 29908014 ↗
L1SR_MA_RCTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[448]
Desai SP, Leatherwood C, Forman M et al.. “Treat-to-Target Approach in Rheumatoid Arthritis: A Quality Improvement Trial.” Arthritis care & research (2021). PMID: 31758663 ↗
L2RCTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[449]
Lopez-Olivo MA, Lin H, Rizvi T et al.. “Randomized Controlled Trial of Patient Education Tools for Patients With Rheumatoid Arthritis.” Arthritis care & research (2021). PMID: 32583971 ↗
L1RCTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[450]
Blalock SJ, Solow EB, Reyna VF et al.. “Enhancing Patient Understanding of Medication Risks and Benefits.” Arthritis care & research (2021). PMID: 32799397 ↗
L1RCTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[451]
Sepriano A, Kerschbaumer A, Bergstra SA et al.. “Safety of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis.” Annals of the rheumatic diseases (2022). PMID: 36376026 ↗
L2SR_OBSCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[452]
Ytterberg SR, Bhatt DL, Mikuls TR et al.. “Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis.” The New England journal of medicine (2022). PMID: 35081280 ↗
L1RCTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment, Prevention, Screening & Surveillance
[453]
Nissen SE, Yeomans ND, Solomon DH et al.. “Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis.” The New England journal of medicine (2016). PMID: 27959716 ↗
L1RCTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment, Prevention, Screening & Surveillance
[454]
Lovell DJ, Ruperto N, Goodman S et al.. “Adalimumab with or without methotrexate in juvenile rheumatoid arthritis.” The New England journal of medicine (2008). PMID: 18716298 ↗
L2RCTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment, Special Populations, Pregnancy & Fertility
[455]
Amaral JK, Sutaria R, Schoen RT. “Treatment of Chronic Chikungunya Arthritis With Methotrexate: A Systematic Review.” Arthritis care & research (2018). PMID: 29361202 ↗
L2SR_OBSCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related
[456]
Lopez-Olivo MA, Kakpovbia-Eshareturi V, des Bordes JK et al.. “Treating Early Undifferentiated Arthritis: A Systematic Review and Meta-Analysis of Direct and Indirect Trial Evidence.” Arthritis care & research (2018). PMID: 29161466 ↗
L1SR_OBSCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[457]
Gossec L, Bessette L, Xavier RM et al.. “Barriers to, Facilitators of, and Interventions to Support Treat-to-Target Implementation in Rheumatoid Arthritis: A Systematic Review.” Arthritis care & research (2024). PMID: 39090845 ↗
L2SR_OBSCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[458]
Smolen JS, Taylor PC, Tanaka Y et al.. “Impact of high rheumatoid factor levels on treatment outcomes with certolizumab pegol and adalimumab in patients with rheumatoid arthritis.” Rheumatology (Oxford, England) (2024). PMID: 39222436 ↗
L2RCTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[459]
Ruiz JI, Lei X, Giordano SH et al.. “Survival in patients with rheumatoid arthritis and recently diagnosed early-stage colorectal, lung, or prostate cancer receiving tumour necrosis factor inhibitors: a retrospective cohort study.” The Lancet. Rheumatology (2025). PMID: 39914441 ↗
L2COHORTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[460]
Burmester GR, Cohen SB, Winthrop KL et al.. “Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis.” RMD open (2023). PMID: 36754548 ↗
L1TRIAL_NONRANDOMCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[461]
Chen Y, Zhang Q, Liu S et al.. “Bidirectional association of rheumatoid arthritis and inflammatory bowel diseases: a large-scale prospective cohort study.” Rheumatology (Oxford, England) (2025). PMID: 40511997 ↗
L2COHORTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[462]
Smolen JS, Landewé R, Bijlsma J et al.. “EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update.” Annals of the rheumatic diseases (2017). PMID: 28264816 ↗
L1REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[463]
Zack SR, Alzoubi O, Satoeya N et al.. “Another Notch in the Belt of Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2024). PMID: 38961731 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[464]
Chin A, Terrett A, Kwon M et al.. “Recommendations for the Use of Disease-Modifying Antirheumatic Drugs in Pregnancy and Reproductive Health for Patients With Rheumatic Disease: A Scoping Review.” Arthritis care & research (2025). PMID: 40256995 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target, Special Populations, Pregnancy & Fertility
[465]
Sparks JA, Lesperance T, Accortt NA et al.. “Subsequent Cardiovascular Events Among Patients With Rheumatoid Arthritis, Psoriatic Arthritis, or Psoriasis: Patterns of Disease-Modifying Antirheumatic Drug Treatment.” Arthritis care & research (2019). PMID: 29799667 ↗
L2OTHERCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[466]
Tan JM, Reeve E, Fraser L et al.. “Barriers and Enablers in the Use of Parenteral Methotrexate in Rheumatoid Arthritis Patients: A Scoping Review.” Arthritis care & research (2023). PMID: 37128818 ↗
L2REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[467]
Fang H, Chen L, Knight JC. “From genome-wide association studies to rational drug target prioritisation in inflammatory arthritis.” The Lancet. Rheumatology (2019). PMID: 38258277 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[468]
Heutz JW, de Jong PHP, Verstappen M et al.. “Sustained DMARD-free remission in subgroups of patients with rheumatoid arthritis: an analysis of two prospective cohorts with early arthritis.” The Lancet. Rheumatology (2024). PMID: 39718182 ↗
L2OTHERCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[469]
Ciancio A, Amati A, Gandolfo S et al.. “Aligning approaches to rheumatoid arthritis drug development: a comparison of FDA and EMA guidance.” The Lancet. Rheumatology (2026). PMID: 42331475 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target, History and Evolution of Treatment
[470]
Scott DL, Wolfe F, Huizinga TW. “Rheumatoid arthritis.” Lancet (London, England) (2010). PMID: 20870100 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target, Special Populations, Pregnancy & Fertility
[471]
Burmester GR, Pope JE. “Novel treatment strategies in rheumatoid arthritis.” Lancet (London, England) (2017). PMID: 28612748 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[472]
Chen J, Liu C, Lin J. “Methotrexate for ankylosing spondylitis.” The Cochrane database of systematic reviews (2006). PMID: 17054209 ↗
L1SR_OBSCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[473]
Lopez-Olivo MA, Amezaga Urruela M, McGahan L et al.. “Rituximab for rheumatoid arthritis.” The Cochrane database of systematic reviews (2015). PMID: 25603545 ↗
L1SR_OBSCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[474]
Ruiz Garcia V, Burls A, Cabello JB et al.. “Certolizumab pegol (CDP870) for rheumatoid arthritis in adults.” The Cochrane database of systematic reviews (2017). PMID: 28884785 ↗
L1SR_OBSCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[475]
Katchamart W, Trudeau J, Phumethum V et al.. “Methotrexate monotherapy versus methotrexate combination therapy with non-biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis.” The Cochrane database of systematic reviews (2010). PMID: 20393970 ↗
L1SR_OBSCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[476]
Ruiz Garcia V, Jobanputra P, Burls A et al.. “Certolizumab pegol (CDP870) for rheumatoid arthritis in adults.” The Cochrane database of systematic reviews (2011). PMID: 21328299 ↗
L1SR_OBSCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[477]
Hazlewood GS, Barnabe C, Tomlinson G et al.. “Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis: A network meta-analysis.” The Cochrane database of systematic reviews (2016). PMID: 27571502 ↗
L1SR_OBSCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[478]
Lethaby A, Lopez-Olivo MA, Maxwell L et al.. “Etanercept for the treatment of rheumatoid arthritis.” The Cochrane database of systematic reviews (2013). PMID: 23728649 ↗
L1SR_OBSCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[479]
Ruiz Garcia V, Jobanputra P, Burls A et al.. “Certolizumab pegol (CDP870) for rheumatoid arthritis in adults.” The Cochrane database of systematic reviews (2014). PMID: 25231904 ↗
L1SR_OBSCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[480]
Clarke B, Yates M, Adas M et al.. “The safety of JAK-1 inhibitors.” Rheumatology (Oxford, England) (2021). PMID: 33950230 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[481]
Nash P. “Clinical use of Jak 1 inhibitors for rheumatoid arthritis.” Rheumatology (Oxford, England) (2021). PMID: 33950231 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[482]
Nouri B, Nair N, Barton A. “Predicting treatment response to IL6R blockers in rheumatoid arthritis.” Rheumatology (Oxford, England) (2020). PMID: 32864695 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[483]
Tanaka Y. “Stopping tumour necrosis factor-targeted biological DMARDs in rheumatoid arthritis.” Rheumatology (Oxford, England) (2016). PMID: 27856656 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[484]
Fragoulis GE, Conway R, Nikiphorou E. “Methotrexate and interstitial lung disease: controversies and questions. A narrative review of the literature.” Rheumatology (Oxford, England) (2019). PMID: 31504978 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[485]
Cronstein BN, Aune TM. “Methotrexate and its mechanisms of action in inflammatory arthritis.” Nature reviews. Rheumatology (2020). PMID: 32066940 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[486]
Winthrop KL. “The emerging safety profile of JAK inhibitors in rheumatic disease.” Nature reviews. Rheumatology (2017). PMID: 28250461 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target, Immunosuppression Safety & Therapeutic Drug Monitoring, Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[487]
Taylor PC, Feldmann M. “Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis.” Nature reviews. Rheumatology (2009). PMID: 19798034 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[488]
Wicks IP, Roberts AW. “Targeting GM-CSF in inflammatory diseases.” Nature reviews. Rheumatology (2015). PMID: 26633290 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[489]
van Vollenhoven R. “Treat-to-target in rheumatoid arthritis - are we there yet?” Nature reviews. Rheumatology (2019). PMID: 30700865 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[490]
Parra Sánchez AR, Voskuyl AE, van Vollenhoven RF. “Treat-to-target in systemic lupus erythematosus: advancing towards its implementation.” Nature reviews. Rheumatology (2022). PMID: 35039665 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[491]
Bertolino GM, Maumus M, Jorgensen C et al.. “Therapeutic potential in rheumatic diseases of extracellular vesicles derived from mesenchymal stromal cells.” Nature reviews. Rheumatology (2023). PMID: 37666995 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[492]
Chan ES, Cronstein BN. “Methotrexate--how does it really work?” Nature reviews. Rheumatology (2010). PMID: 20197777 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[493]
Winthrop KL, Cohen SB. “Oral surveillance and JAK inhibitor safety: the theory of relativity.” Nature reviews. Rheumatology (2022). PMID: 35318462 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[494]
Gunkl-Tóth L, McInnes IB, Nagy G. “Bridging the gap: combining treat-to-target and difficult-to-treat strategies in the management of rheumatoid arthritis.” Nature reviews. Rheumatology (2026). PMID: 41772290 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[495]
Cho IY, Jung JH, Kang S et al.. “Rheumatoid arthritis and risk of myocardial infarction: A nationwide cohort study.” European journal of preventive cardiology (2026). PMID: 42429686 ↗
L2COHORTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[496]
Pope JE. “Management of Fatigue in Rheumatoid Arthritis.” RMD open (2020). PMID: 32385141 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[497]
Manara M, Sinigaglia L. “Bone and TNF in rheumatoid arthritis: clinical implications.” RMD open (2015). PMID: 26557382 ↗
L5REVIEW_NARRATIVECited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[498]
Teng Y, Yin H, Feng R et al.. “Methotrexate inhibits glucocorticoids-induced osteoclastogenesis via activating IFN-γR/STAT1 pathway in the treatment of rheumatoid arthritis.” RMD open (2024). PMID: 39510764 ↗
L5OTHERCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related
[499]
Hooker RS, Reinhart GM. “Trends in DMARD prescribing by rheumatologists, NPs, and PAs among medicare beneficiaries, 2013-2023: an observational retrospective cohort study.” Rheumatology international (2026). PMID: 42334644 ↗
L2COHORTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[500]
Murata K, Fujii T, Ebina K et al.. “Real-world clinical outcomes of patients with disproportionate articular pain in rheumatoid arthritis: ANSWER cohort study.” Scandinavian journal of rheumatology (2026). PMID: 42318602 ↗
L2COHORTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[501]
Pan X, Tian J, Chen J et al.. “Correction: Clinical characteristics and risk factors of severe myelosuppression in rheumatoid arthritis patients with csDMARD non-adherence: a case series.” Frontiers in pharmacology (2026). PMID: 42318336 ↗
L4CASE_REPORTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[502]
Lini D, Colina M, Andracco R et al.. “Real-World Effectiveness of Baricitinib in Rheumatoid Arthritis: Significant Reduction of Disease Activity Independent of Age in a Multicentre Retrospective Cohort Study.” Mediterranean journal of rheumatology (2026). PMID: 42368989 ↗
L3COHORTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target
[503]
Yamashita Y, Maeda K, Okabe H et al.. “Long-term longitudinal changes in bone matrix and turnover markers in rheumatoid arthritis: A retrospective cohort study.” Medicine (2026). PMID: 42332458 ↗
L3COHORTCited in: Long-term Management: The DMARD Ladder & Treat-to-Target, Complications: Disease-Driven & Treatment-Related
[504]
Tamai H, Ikeda K, Miyamoto T et al.. “Association of methotrexate polyglutamates concentration with methotrexate efficacy and safety in patients with rheumatoid arthritis treated with predefined dose: results from the MIRACLE trial.” Annals of the rheumatic diseases (2025). PMID: 39874232 ↗
L1RCTCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[505]
Taylor PC, Weinblatt ME, McInnes IB et al.. “Anti-GM-CSF otilimab versus sarilumab or placebo in patients with rheumatoid arthritis and inadequate response to targeted therapies: a phase III randomised trial (contRAst 3).” Annals of the rheumatic diseases (2023). PMID: 37696589 ↗
L1RCTCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[506]
Fleischmann RM, van der Heijde D, Strand V et al.. “Anti-GM-CSF otilimab versus tofacitinib or placebo in patients with active rheumatoid arthritis and an inadequate response to conventional or biologic DMARDs: two phase 3 randomised trials (contRAst 1 and contRAst 2).” Annals of the rheumatic diseases (2023). PMID: 37699654 ↗
L1TRIAL_NONRANDOMCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[507]
Taylor PC, Takeuchi T, Burmester GR et al.. “Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database.” Annals of the rheumatic diseases (2021). PMID: 34706874 ↗
L2SR_OBSCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[508]
Nam JL, Winthrop KL, van Vollenhoven RF et al.. “Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA.” Annals of the rheumatic diseases (2010). PMID: 20447957 ↗
L1SR_OBSCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[509]
Konzett V, Laskou F, Smolen JS et al.. “Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2025 update of the EULAR recommendations for the management of rheumatoid arthritis.” Annals of the rheumatic diseases (2026). PMID: 41997804 ↗
L1SR_OBSCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[510]
Buch MH, Smolen JS, Betteridge N et al.. “Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis.” Annals of the rheumatic diseases (2011). PMID: 21378402 ↗
L1SR_OBSCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[511]
Akiyama S, Hamdeh S, Micic D et al.. “Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis.” Annals of the rheumatic diseases (2020). PMID: 33051220 ↗
L2SR_OBSCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[512]
Ye BD, Pesegova M, Alexeeva O et al.. “Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study.” Lancet (London, England) (2019). PMID: 30929895 ↗
L1RCTCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[513]
Agueusop I, Margerie D, Remaury A et al.. “Deciphering differential biomarkers for anti-interleukin-6 receptor and anti-tumour necrosis factor-α treatment response in rheumatoid arthritis by multiomics analysis.” RMD open (2025). PMID: 40759562 ↗
L3RCTCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[514]
Zubrzycka-Sienkiewicz A, Klama K, Ullmann M et al.. “Comparison of the efficacy and safety of a proposed biosimilar MSB11456 with tocilizumab reference product in subjects with moderate-to-severe rheumatoid arthritis: results of a randomised double-blind study.” RMD open (2024). PMID: 38316489 ↗
L1RCTCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[515]
Farisogullari B, Santos EJF, Dures E et al.. “Efficacy of pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.” RMD open (2023). PMID: 38056919 ↗
L1SR_OBSCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[516]
Triboulet F, Juge PA, Truchetet ME et al.. “Evaluation of rheumatoid arthritis-associated interstitial lung disease in patients treated with JAK inhibitors: a MAJIK-SFR cohort study.” RMD open (2025). PMID: 39762124 ↗
L2COHORTCited in: Immunosuppression Safety & Therapeutic Drug Monitoring, Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[517]
Tanaka Y, Hanami K, Miyazaki Y et al.. “Real-world effectiveness, safety and patient-reported outcomes of sarilumab in patients with rheumatoid arthritis: a 52-week, prospective, open-label, non-interventional, observational, nationwide, large-cohort study in Japan (PROFILE-J).” RMD open (2026). PMID: 42120177 ↗
L2COHORTCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[518]
Bower H, Frisell T, di Giuseppe D et al.. “Comparative cardiovascular safety with janus kinase inhibitors and biological disease-modifying antirheumatic drugs as used in clinical practice: an observational cohort study from Sweden in patients with rheumatoid arthritis.” RMD open (2023). PMID: 37996125 ↗
L2COHORTCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[519]
Beauvais C, Fayet F, Rousseau A et al.. “Efficacy of a nurse-led patient education intervention in promoting safety skills of patients with inflammatory arthritis treated with biologics: a multicentre randomised clinical trial.” RMD open (2022). PMID: 35296528 ↗
L1RCTCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[520]
Syversen SW, Jørgensen KK, Goll GL et al.. “Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial.” JAMA (2021). PMID: 34932077 ↗
L1RCTCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[521]
Rigby W, Buckner JH, Louis Bridges S et al.. “HLA-DRB1 risk alleles for RA are associated with differential clinical responsiveness to abatacept and adalimumab: data from a head-to-head, randomized, single-blind study in autoantibody-positive early RA.” Arthritis research & therapy (2021). PMID: 34537057 ↗
L1RCTCited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[522]
Rubbert-Roth A. “Assessing the safety of biologic agents in patients with rheumatoid arthritis.” Rheumatology (Oxford, England) (2012). PMID: 22718926 ↗
L5REVIEW_NARRATIVECited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[523]
Jorge A, Ung C, Young LH et al.. “Hydroxychloroquine retinopathy - implications of research advances for rheumatology care.” Nature reviews. Rheumatology (2018). PMID: 30401979 ↗
L5REVIEW_NARRATIVECited in: Immunosuppression Safety & Therapeutic Drug Monitoring
[524]
Riley TR, George MD. “Risk for infections with glucocorticoids and DMARDs in patients with rheumatoid arthritis.” RMD open (2021). PMID: 33597206 ↗
L5REVIEW_NARRATIVECited in: Immunosuppression Safety & Therapeutic Drug Monitoring, Complications: Disease-Driven & Treatment-Related
[525]
Antoniou KM, Distler O, Gheorghiu AM et al.. “ERS/EULAR clinical practice guidelines for connective tissue disease-associated interstitial lung disease developed by the task force for connective tissue disease-associated interstitial lung disease of the European Respiratory Society (ERS) and the European Alliance of Associations for Rheumatology (EULAR) Endorsed by the European Reference Network on rare respiratory diseases (ERN-LUNG).” Annals of the rheumatic diseases (2025). PMID: 40912974 ↗
L1GUIDELINECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), History and Evolution of Treatment, Prevention, Screening & Surveillance
[526]
Johnson SR, Bernstein EJ, Bolster MB et al.. “2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.” Arthritis care & research (2024). PMID: 38973729 ↗
L1GUIDELINECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), History and Evolution of Treatment, Prevention, Screening & Surveillance
[527]
Shirai Y, Honda S, Ikari K et al.. “Association of the RPA3-UMAD1 locus with interstitial lung diseases complicated with rheumatoid arthritis in Japanese.” Annals of the rheumatic diseases (2020). PMID: 32737115 ↗
L3SR_OBSCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[528]
Hyldgaard C, Hilberg O, Pedersen AB et al.. “A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality.” Annals of the rheumatic diseases (2017). PMID: 28611082 ↗
L2COHORTCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[529]
Kimbrough BA, Crowson CS, Davis JM et al.. “Decline in Incidence of Extra-Articular Manifestations of Rheumatoid Arthritis: A Population-Based Cohort Study.” Arthritis care & research (2023). PMID: 37691141 ↗
L2COHORTCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[530]
Russell MD, Schaffer A, Yang Z et al.. “Trends in autoimmune rheumatic disease diagnoses before and after the COVID-19 pandemic in England: a population-based cohort study using OpenSAFELY.” The Lancet. Rheumatology (2026). PMID: 42379213 ↗
L2COHORTCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[531]
England BR, Baker JF, George MD et al.. “Advanced therapies in US veterans with rheumatoid arthritis-associated interstitial lung disease: a retrospective, active-comparator, new-user, cohort study.” The Lancet. Rheumatology (2025). PMID: 39793598 ↗
L2COHORTCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[532]
Figueroa-Parra G, Gilbert EL, Valenzuela-Almada MO et al.. “Risk of severe COVID-19 outcomes associated with rheumatoid arthritis and phenotypic subgroups: a retrospective, comparative, multicentre cohort study.” The Lancet. Rheumatology (2022). PMID: 36118532 ↗
L2COHORTCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[533]
Avouac J, Drumez E, Hachulla E et al.. “COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study.” The Lancet. Rheumatology (2021). PMID: 33786454 ↗
L2COHORTCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[534]
Md Yusof MY, Arnold J, Saleem B et al.. “Breakthrough SARS-CoV-2 infections and prediction of moderate-to-severe outcomes during rituximab therapy in patients with rheumatic and musculoskeletal diseases in the UK: a single-centre cohort study.” The Lancet. Rheumatology (2023). PMID: 36712951 ↗
L2COHORTCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), Complications: Disease-Driven & Treatment-Related
[535]
Matteson EL, Matucci-Cerinic M, Kreuter M et al.. “Patient-level factors predictive of interstitial lung disease in rheumatoid arthritis: a systematic review.” RMD open (2023). PMID: 37507209 ↗
L2SR_OBSCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[536]
Rosa-Baez C, Rangel-Pelaez C, Rodriguez-Martin I et al.. “Assessing the MUC5B promoter variant in a large cohort of systemic sclerosis-associated interstitial lung disease.” RMD open (2025). PMID: 40803819 ↗
L3SR_OBSCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[537]
Yuan H, Cui S, Yang L et al.. “Efficacy of non-conventional synthetic DMARDs for patients with rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.” RMD open (2023). PMID: 37899093 ↗
L2SR_OBSCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[538]
Joo YB, Ahn SM, Bang SY et al.. “MUC5B promoter variant rs35705950, rare but significant susceptibility locus in rheumatoid arthritis-interstitial lung disease with usual interstitial pneumonia in Asian populations.” RMD open (2022). PMID: 36581384 ↗
L3SR_OBSCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[539]
Kronzer VL, Williamson KA, Hayashi K et al.. “Uncovering specific genetic-respiratory disease endotypes for rheumatoid arthritis risk.” Annals of the rheumatic diseases (2025). PMID: 39919896 ↗
L3OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[540]
Tanaka H, Okada Y, Nakayamada S et al.. “Extracting immunological and clinical heterogeneity across autoimmune rheumatic diseases by cohort-wide immunophenotyping.” Annals of the rheumatic diseases (2024). PMID: 37903543 ↗
L4OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[541]
Winthrop KL, Mease P, Kerschbaumer A et al.. “Unmet need in rheumatology: reports from the Advances in Targeted Therapies meeting, 2023.” Annals of the rheumatic diseases (2024). PMID: 38123338 ↗
L5OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[542]
Winthrop KL, Weinblatt ME, Bathon J et al.. “Unmet need in rheumatology: reports from the Targeted Therapies meeting 2019.” Annals of the rheumatic diseases (2019). PMID: 31662322 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[543]
van Mourik AG, Keijser JBD, van Delft MAM et al.. “Dimerization as a key feature of autoreactive IgA antibody responses.” Annals of the rheumatic diseases (2025). PMID: 41318346 ↗
L3OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[544]
Winthrop KL, Weinblatt ME, Crow MK et al.. “Unmet need in rheumatology: reports from the Targeted Therapies meeting 2018.” Annals of the rheumatic diseases (2019). PMID: 30712015 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[545]
Palomäki A, Palotie A, Koskela J et al.. “Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers.” Annals of the rheumatic diseases (2021). PMID: 34344703 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[546]
Tang X, Peng Y, Jiang Z et al.. “Efferocytosis and Its Role in Rheumatic Diseases.” Arthritis & rheumatology (Hoboken, N.J.) (2025). PMID: 40452369 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[547]
Shih PC, Wang SI, Wei JCC. “Association of Abatacept With Lower Mortality Risk Compared to Rituximab in Rheumatoid Arthritis-Associated Interstitial Lung Disease: An Emulated Target Trial.” Arthritis & rheumatology (Hoboken, N.J.) (2025). PMID: 40693411 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), Complications: Disease-Driven & Treatment-Related
[548]
Brooks RT, Luedders B, Wheeler A et al.. “The Risk of Lung Cancer in Rheumatoid Arthritis and Rheumatoid Arthritis-Associated Interstitial Lung Disease.” Arthritis & rheumatology (Hoboken, N.J.) (2024). PMID: 39073264 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[549]
Spagnolo P, Lee JS, Sverzellati N et al.. “The Lung in Rheumatoid Arthritis: Focus on Interstitial Lung Disease.” Arthritis & rheumatology (Hoboken, N.J.) (2018). PMID: 29806092 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[550]
Suga K, Seng A, Yao C et al.. “Single-Cell Analysis Reveals Peripheral Helper T Cells in Rheumatoid Arthritis-Related Interstitial Lung Disease.” Arthritis & rheumatology (Hoboken, N.J.) (2026). PMID: 41629202 ↗
L4OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[551]
Kronzer VL, Yang Y, Roul P et al.. “Associations of Fire Smoke and Other Pollutants With Incident Rheumatoid Arthritis and Rheumatoid Arthritis-Associated Interstitial Lung Disease.” Arthritis & rheumatology (Hoboken, N.J.) (2025). PMID: 39800945 ↗
L3OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[552]
Chen J, Doyle TJ, Liu Y et al.. “Biomarkers of rheumatoid arthritis-associated interstitial lung disease.” Arthritis & rheumatology (Hoboken, N.J.) (2015). PMID: 25302945 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[553]
Fava A, Wagner CA, Guthridge CJ et al.. “Serum Soluble Mediator Signatures of Lupus Nephritis: Histologic Features and Response to Treatment.” Arthritis care & research (2025). PMID: 41048053 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[554]
Coziahr K, Wheeler AM, Luedders BA et al.. “Combining Three Peripheral Blood Biomarkers to Stratify Rheumatoid Arthritis-Associated Interstitial Lung Disease Risk.” Arthritis care & research (2025). PMID: 41392523 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[555]
England BR, Roul P, Mahajan TD et al.. “Performance of Administrative Algorithms to Identify Interstitial Lung Disease in Rheumatoid Arthritis.” Arthritis care & research (2020). PMID: 31421018 ↗
L3OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[556]
Eder L, Croxford R, Drucker AM et al.. “Understanding COVID-19 Risk in Patients With Immune-Mediated Inflammatory Diseases: A Population-Based Analysis of SARS-CoV-2 Testing.” Arthritis care & research (2022). PMID: 34486829 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[557]
Samhouri BF, Vassallo R, Achenbach SJ et al.. “Incidence, Risk Factors, and Mortality of Clinical and Subclinical Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Population-Based Cohort.” Arthritis care & research (2022). PMID: 34995017 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[558]
Dharia T, Venkatachalam S, Baker JF et al.. “Medication Interruptions and Subsequent Disease Flares During the COVID-19 Pandemic: A Longitudinal Online Study of Patients With Rheumatic Disease.” Arthritis care & research (2022). PMID: 34890121 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[559]
Droz N, Gilardin L, Cacoub P et al.. “Kinetic profiles and management of hepatitis B virus reactivation in patients with immune-mediated inflammatory diseases.” Arthritis care & research (2013). PMID: 23436730 ↗
L4REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[560]
Nannini C, Medina-Velasquez YF, Achenbach SJ et al.. “Incidence and mortality of obstructive lung disease in rheumatoid arthritis: a population-based study.” Arthritis care & research (2013). PMID: 23436637 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[561]
Cooles FAH, Isaacs JD. “The interferon gene signature as a clinically relevant biomarker in autoimmune rheumatic disease.” The Lancet. Rheumatology (2021). PMID: 38288732 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[562]
Juge PA, Lee JS, Ebstein E et al.. “MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease.” The New England journal of medicine (2018). PMID: 30345907 ↗
L3OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[563]
Li M, Wang Q, He J et al.. “A machine learning-based classification model for interstitial lung disease in rheumatoid arthritis.” Frontiers in medicine (2026). PMID: 42221109 ↗
L3TRIAL_NONRANDOMCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), History and Evolution of Treatment
[564]
Gustafsson AL, Heckemann RA, Erlandsson MC et al.. “Handgrip weakness is associated with motor cortex atrophy in rheumatoid arthritis: a cross-sectional study with a hand exercise intervention.” BMC medicine (2026). PMID: 42192374 ↗
L4TRIAL_NONRANDOMCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[565]
Barnes H, Holland AE, Westall GP et al.. “Cyclophosphamide for connective tissue disease-associated interstitial lung disease.” The Cochrane database of systematic reviews (2018). PMID: 29297205 ↗
L1SR_OBSCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[566]
Chioni A, Campochiaro C, Keret S et al.. “Nintedanib combined with dual immunosuppression for interstitial lung disease in systemic sclerosis and rheumatoid arthritis: A systematic review and pooled multicentre real-world cohort study.” Autoimmunity reviews (2026). PMID: 42162630 ↗
L2SR_OBSCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[567]
Serrano-Combarro A, Atienza-Mateo B, Martín-Gutiérrez A et al.. “Baricitinib in rheumatoid arthritis-interstitial lung disease: a literature review and national multicentre study of 72 patients.” Rheumatology (Oxford, England) (2025). PMID: 40493905 ↗
L4REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[568]
Zhang Q, Qi Y, Wang X et al.. “Risk of total and cause-specific mortality in patients with rheumatoid arthritis-associated interstitial lung disease or bronchiectasis.” Rheumatology (Oxford, England) (2025). PMID: 40644608 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[569]
Catrina AI, Deane KD, Scher JU. “Gene, environment, microbiome and mucosal immune tolerance in rheumatoid arthritis.” Rheumatology (Oxford, England) (2014). PMID: 25539828 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[570]
Chang SH, Lee JS, Ha YJ et al.. “Lung function trajectory of rheumatoid arthritis-associated interstitial lung disease.” Rheumatology (Oxford, England) (2023). PMID: 36702465 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[571]
Black RJ, Lester S, Tieu J et al.. “Mortality estimates and excess mortality in rheumatoid arthritis.” Rheumatology (Oxford, England) (2023). PMID: 36919770 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[572]
Esposito AJ, Sparks JA, Gill RR et al.. “Screening for preclinical parenchymal lung disease in rheumatoid arthritis.” Rheumatology (Oxford, England) (2022). PMID: 34875040 ↗
L2OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), Prevention, Screening & Surveillance
[573]
Perry E, Kelly C, Eggleton P et al.. “The lung in ACPA-positive rheumatoid arthritis: an initiating site of injury?” Rheumatology (Oxford, England) (2014). PMID: 24831057 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[574]
Segelmark M. “Serological testing in small vessel vasculitis.” Rheumatology (Oxford, England) (2020). PMID: 32348521 ↗
L5OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[575]
Wang D, Zhang J, Lau J et al.. “Mechanisms of lung disease development in rheumatoid arthritis.” Nature reviews. Rheumatology (2019). PMID: 31455869 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[576]
Buch MH, Mallat Z, Dweck MR et al.. “Current understanding and management of cardiovascular involvement in rheumatic immune-mediated inflammatory diseases.” Nature reviews. Rheumatology (2024). PMID: 39232242 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[577]
Wells AU, Denton CP. “Interstitial lung disease in connective tissue disease--mechanisms and management.” Nature reviews. Rheumatology (2014). PMID: 25266451 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[578]
Szekanecz Z, Gunkl-Tóth L, Szamosi S et al.. “Diagnostic, prognostic and therapeutic biomarkers in rheumatoid arthritis.” Nature reviews. Rheumatology (2026). PMID: 42298194 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[579]
Stanford SM, Bottini N. “PTPN22: the archetypal non-HLA autoimmunity gene.” Nature reviews. Rheumatology (2014). PMID: 25003765 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[580]
Artifoni M, Rothschild PR, Brézin A et al.. “Ocular inflammatory diseases associated with rheumatoid arthritis.” Nature reviews. Rheumatology (2013). PMID: 24323074 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[581]
Brooks RT, England BR, Kronzer VL et al.. “The evolving comorbidity landscape of rheumatoid arthritis.” Nature reviews. Rheumatology (2026). PMID: 42215625 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[582]
Jani M, Hirani N, Matteson EL et al.. “The safety of biologic therapies in RA-associated interstitial lung disease.” Nature reviews. Rheumatology (2013). PMID: 24366321 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[583]
Miyabe Y, Lian J, Miyabe C et al.. “Chemokines in rheumatic diseases: pathogenic role and therapeutic implications.” Nature reviews. Rheumatology (2019). PMID: 31705045 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[584]
Aringer M, Distler O, Hoffmann-Vold AM et al.. “Rationale for phosphodiesterase-4 inhibition as a treatment strategy for interstitial lung diseases associated with rheumatic diseases.” RMD open (2024). PMID: 39719300 ↗
L5REVIEW_NARRATIVECited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[585]
Vermant M, Kalkanis A, Jacob J et al.. “Lung ultrasound outperforms symptom-based screening to detect interstitial lung disease associated with rheumatoid arthritis.” RMD open (2025). PMID: 40010942 ↗
L1OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[586]
Kim SH, Kim SY, Yoon HY et al.. “PM10 increases mortality risk in rheumatoid arthritis-associated interstitial lung disease.” RMD open (2024). PMID: 38331470 ↗
L3OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[587]
Higuchi T, Oka S, Furukawa H et al.. “Association of a FAM13A variant with interstitial lung disease in Japanese rheumatoid arthritis.” RMD open (2023). PMID: 36717188 ↗
L3OTHERCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[588]
Zhenyan B, Huang L, Lu J et al.. “The pharmacokinetics and its covariates of rituximab in different clinical populations: a systematic review and narrative synthesis.” European journal of clinical pharmacology (2026). PMID: 42426484 ↗
L2SR_OBSCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[589]
Du D, Qin J, Zhang G et al.. “Diagnostic accuracy of lung ultrasound in identifying connective tissue disease related interstitial lung disease: a systematic review and meta-analysis.” Clinical and experimental rheumatology (2026). PMID: 42370501 ↗
L1SR_OBSCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[590]
Qiaoqian Z, Qing W, Bowen L et al.. “Tumor markers in rheumatoid arthritis -associated interstitial lung disease: a systematic review and meta-analysis.” BMC rheumatology (2026). PMID: 42337778 ↗
L3SR_OBSCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[591]
Qi S, Jiang Y, Li H et al.. “Detection of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.” BMC pulmonary medicine (2026). PMID: 42324528 ↗
L1SR_OBSCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map), Prevention, Screening & Surveillance
[592]
Yamane T, Inoue A, Yasuda N et al.. “Real-world retention of nintedanib and factors associated with treatment discontinuation in connective tissue disease-associated interstitial lung disease: a retrospective cohort study of 92 patients.” Clinical rheumatology (2026). PMID: 42402543 ↗
L4COHORTCited in: Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)
[593]
Liu J, Jiang Y, Zhang S et al.. “Ivarmacitinib, a selective Janus kinase 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis and inadequate response to conventional synthetic DMARDs: results from a phase III randomised clinical trial.” Annals of the rheumatic diseases (2025). PMID: 39919893 ↗
L1RCTCited in: Complications: Disease-Driven & Treatment-Related
[594]
Sebbag E, Molina-Collada J, Ndoye R et al.. “Systematic literature review and meta-analysis informing the EULAR points to consider on the initiation of targeted therapies in patients with inflammatory arthritis and a history of cancer.” Annals of the rheumatic diseases (2025). PMID: 39739386 ↗
L2SR_OBSCited in: Complications: Disease-Driven & Treatment-Related
[595]
Vanags D, Williams B, Johnson B et al.. “Therapeutic efficacy and safety of chaperonin 10 in patients with rheumatoid arthritis: a double-blind randomised trial.” Lancet (London, England) (2006). PMID: 16950363 ↗
L1RCTCited in: Complications: Disease-Driven & Treatment-Related
[596]
Smolen JS, Burmester GR, Combe B et al.. “Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid arthritis: 2-year efficacy and safety results from the randomised EXXELERATE study.” Lancet (London, England) (2016). PMID: 27863807 ↗
L1RCTCited in: Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[597]
Zhang Q, Qi Y, Wang X et al.. “Risk of Serious Infection in Patients With Rheumatoid Arthritis-Associated Interstitial Lung Disease or Bronchiectasis: A Comparative Cohort Study.” Arthritis & rheumatology (Hoboken, N.J.) (2025). PMID: 40708472 ↗
L3COHORTCited in: Complications: Disease-Driven & Treatment-Related
[598]
Beltai A, Barnetche T, Daien C et al.. “Cardiovascular Morbidity and Mortality in Primary Sjögren's Syndrome: A Systematic Review and Meta-Analysis.” Arthritis care & research (2020). PMID: 30570824 ↗
L2SR_OBSCited in: Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[599]
Mathieu S, Gossec L, Dougados M et al.. “Cardiovascular profile in ankylosing spondylitis: a systematic review and meta-analysis.” Arthritis care & research (2011). PMID: 20890982 ↗
L2SR_OBSCited in: Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[600]
Wetzman A, Lukas C, Gaujoux-Viala C et al.. “Risk of Cancer After Initiation of Targeted Therapies in Patients With Rheumatoid Arthritis and a Prior Cancer: Systematic Review With Meta-Analysis.” Arthritis care & research (2022). PMID: 34549898 ↗
L2SR_OBSCited in: Complications: Disease-Driven & Treatment-Related, History and Evolution of Treatment
[601]
Lin TC, Yoshida K, Tedeschi SK et al.. “Risk of Hepatitis B Virus Reactivation in Patients With Inflammatory Arthritis Receiving Disease-Modifying Antirheumatic Drugs: A Systematic Review and Meta-Analysis.” Arthritis care & research (2018). PMID: 28834412 ↗
L2SR_OBSCited in: Complications: Disease-Driven & Treatment-Related
[602]
Singh S, Fumery M, Singh AG et al.. “Comparative Risk of Cardiovascular Events With Biologic and Synthetic Disease-Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.” Arthritis care & research (2020). PMID: 30875456 ↗
L2SR_OBSCited in: Complications: Disease-Driven & Treatment-Related
[603]
Hanberg JS, Fu X, Wang X et al.. “Effectiveness of a fourth dose of COVID-19 mRNA vaccine in patients with systemic autoimmune rheumatic diseases using disease-modifying antirheumatic drugs: an emulated target trial.” The Lancet. Rheumatology (2023). PMID: 38258675 ↗
L2TRIAL_NONRANDOMCited in: Complications: Disease-Driven & Treatment-Related
[604]
Singh JA, Cameron C, Noorbaloochi S et al.. “Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis.” Lancet (London, England) (2015). PMID: 25975452 ↗
L1SR_OBSCited in: Complications: Disease-Driven & Treatment-Related
[605]
Gentry CA, Humphrey MB, Thind SK et al.. “Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study.” The Lancet. Rheumatology (2020). PMID: 32984847 ↗
L2COHORTCited in: Complications: Disease-Driven & Treatment-Related
[606]
Kameda H, Takeuchi T, Yamaoka K et al.. “Long-term safety and efficacy of upadacitinib in Japanese patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: 5-year results from the SELECT-SUNRISE randomised controlled trial.” RMD open (2025). PMID: 41193232 ↗
L1RCTCited in: Complications: Disease-Driven & Treatment-Related
[607]
Cao S, Li Y, Song R et al.. “L-arginine metabolism inhibits arthritis and inflammatory bone loss.” Annals of the rheumatic diseases (2024). PMID: 37775153 ↗
L5OTHERCited in: Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[608]
Hoshida Y, Tsujii A, Ohshima S et al.. “Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders.” Arthritis & rheumatology (Hoboken, N.J.) (2024). PMID: 38272827 ↗
L4OTHERCited in: Complications: Disease-Driven & Treatment-Related
[609]
Frank KM, Hogarth DK, Miller JL et al.. “Investigation of the cause of death in a gene-therapy trial.” The New England journal of medicine (2009). PMID: 19587341 ↗
L4CASE_REPORTCited in: Complications: Disease-Driven & Treatment-Related
[610]
Yun H, Chen L, Roy JA et al.. “Rheumatoid Arthritis Disease Activity and Hospitalized Infection in a Large US Registry.” Arthritis care & research (2023). PMID: 35866713 ↗
L2OTHERCited in: Complications: Disease-Driven & Treatment-Related
[611]
Curtis JR, Yang S, Singh JA et al.. “Is Rheumatoid Arthritis a Cardiovascular Risk-Equivalent to Diabetes Mellitus?” Arthritis care & research (2018). PMID: 29409152 ↗
L2OTHERCited in: Complications: Disease-Driven & Treatment-Related
[612]
Garcia-Montoya L, Villota-Eraso C, Yusof MYM et al.. “Lessons for rituximab therapy in patients with rheumatoid arthritis.” The Lancet. Rheumatology (2020). PMID: 38273611 ↗
L5REVIEW_NARRATIVECited in: Complications: Disease-Driven & Treatment-Related
[613]
Widdifield J, Kwong JC, Chen S et al.. “Vaccine effectiveness against SARS-CoV-2 infection and severe outcomes among individuals with immune-mediated inflammatory diseases tested between March 1 and Nov 22, 2021, in Ontario, Canada: a population-based analysis.” The Lancet. Rheumatology (2022). PMID: 35441151 ↗
L3OTHERCited in: Complications: Disease-Driven & Treatment-Related
[614]
Frisoni GB, Aho E, Brayne C et al.. “Alzheimer's disease outlook: controversies and future directions.” Lancet (London, England) (2025). PMID: 40997840 ↗
L5REVIEW_NARRATIVECited in: Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[615]
Singh JA, Wells GA, Christensen R et al.. “Adverse effects of biologics: a network meta-analysis and Cochrane overview.” The Cochrane database of systematic reviews (2011). PMID: 21328309 ↗
L1SR_OBSCited in: Complications: Disease-Driven & Treatment-Related
[616]
Hagen KB, Byfuglien MG, Falzon L et al.. “Dietary interventions for rheumatoid arthritis.” The Cochrane database of systematic reviews (2009). PMID: 19160281 ↗
L1SR_OBSCited in: Complications: Disease-Driven & Treatment-Related
[617]
Tuntland H, Kjeken I, Nordheim LV et al.. “Assistive technology for rheumatoid arthritis.” The Cochrane database of systematic reviews (2009). PMID: 19821383 ↗
L1SR_OBSCited in: Complications: Disease-Driven & Treatment-Related
[618]
Whittle SL, Richards BL, Husni E et al.. “Opioid therapy for treating rheumatoid arthritis pain.” The Cochrane database of systematic reviews (2011). PMID: 22071805 ↗
L1SR_OBSCited in: Complications: Disease-Driven & Treatment-Related
[619]
Richards BL, Whittle SL, Buchbinder R. “Antidepressants for pain management in rheumatoid arthritis.” The Cochrane database of systematic reviews (2011). PMID: 22071859 ↗
L1SR_OBSCited in: Complications: Disease-Driven & Treatment-Related
[620]
Baker JF, England BR, George MD et al.. “Elevations in adipocytokines and mortality in rheumatoid arthritis.” Rheumatology (Oxford, England) (2022). PMID: 35325041 ↗
L2OTHERCited in: Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[621]
McDonnell T, Ioannou Y, Rahman A. “PEGylated drugs in rheumatology--why develop them and do they work?” Rheumatology (Oxford, England) (2013). PMID: 23962623 ↗
L5REVIEW_NARRATIVECited in: Complications: Disease-Driven & Treatment-Related
[622]
Liao KP, Solomon DH. “Traditional cardiovascular risk factors, inflammation and cardiovascular risk in rheumatoid arthritis.” Rheumatology (Oxford, England) (2012). PMID: 22986289 ↗
L5REVIEW_NARRATIVECited in: Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[623]
Listing J, Gerhold K, Zink A. “The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment.” Rheumatology (Oxford, England) (2012). PMID: 23192911 ↗
L5REVIEW_NARRATIVECited in: Complications: Disease-Driven & Treatment-Related
[624]
Kiely PDW, Lloyd ME. “Ankle arthritis - an important signpost in rheumatologic practice.” Rheumatology (Oxford, England) (2021). PMID: 33097958 ↗
L5REVIEW_NARRATIVECited in: Complications: Disease-Driven & Treatment-Related
[625]
Robinson WH, Younis S, Love ZZ et al.. “Epstein-Barr virus as a potentiator of autoimmune diseases.” Nature reviews. Rheumatology (2024). PMID: 39390260 ↗
L5REVIEW_NARRATIVECited in: Complications: Disease-Driven & Treatment-Related
[626]
Komatsu N, Takayanagi H. “Mechanisms of joint destruction in rheumatoid arthritis - immune cell-fibroblast-bone interactions.” Nature reviews. Rheumatology (2022). PMID: 35705856 ↗
L5REVIEW_NARRATIVECited in: Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[627]
Tuckermann J, Adams RH. “The endothelium-bone axis in development, homeostasis and bone and joint disease.” Nature reviews. Rheumatology (2021). PMID: 34480164 ↗
L5REVIEW_NARRATIVECited in: Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[628]
Lochhead RB, Strle K, Arvikar SL et al.. “Lyme arthritis: linking infection, inflammation and autoimmunity.” Nature reviews. Rheumatology (2021). PMID: 34226730 ↗
L5REVIEW_NARRATIVECited in: Complications: Disease-Driven & Treatment-Related
[629]
Rákóczi É, Szekanecz Z. “Pneumococcal vaccination in autoimmune rheumatic diseases.” RMD open (2017). PMID: 28955497 ↗
L5REVIEW_NARRATIVECited in: Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[630]
Beretta M, Martin E, Fogel O et al.. “Adaptive immune responses to SARS-CoV-2 in DMARD-treated patients with chronic inflammatory rheumatisms.” RMD open (2025). PMID: 40617588 ↗
L4OTHERCited in: Complications: Disease-Driven & Treatment-Related
[631]
Kachhadia MP, Puri P, Patel K et al.. “Sodium-Glucose Co-Transporter 2 Inhibitor Use and Risk of Major Adverse Cardiovascular Events in Patients With Rheumatoid Arthritis and Type 2 Diabetes: A Retrospective Observational Cohort Study Using Real-World Data.” Journal of clinical medicine research (2026). PMID: 42327973 ↗
L2COHORTCited in: Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[632]
Taylor-Williams O, Wall CJ, Nossent J et al.. “Revision Risk Following Total Hip Arthroplasty in Patients With Rheumatoid Arthritis: A Cohort Study From the Australian Orthopaedic Association National Joint Replacement Registry.” ANZ journal of surgery (2026). PMID: 42316895 ↗
L2COHORTCited in: Complications: Disease-Driven & Treatment-Related, Special Populations, Pregnancy & Fertility
[633]
Paparozzi J, Barroca C, Gogerdchian H et al.. “Nutraceutical enhancement of paraoxonase 1 activity in chronic inflammation: A systematic review of animal-based and plant-based nutraceuticals.” Nutrition and health (2026). PMID: 42393907 ↗
L5SR_OBSCited in: Complications: Disease-Driven & Treatment-Related, Prevention, Screening & Surveillance
[634]
Cook JA, Wilson N, Wilkins K et al.. “Clinical and cost-effectiveness of oral versus intramuscular glucocorticoids in rheumatoid arthritis: protocol for a multicentre randomised controlled trial with economic evaluation and qualitative sub-study (LEADER trial).” BMJ open (2026). PMID: 42431665 ↗
L5OTHERCited in: Complications: Disease-Driven & Treatment-Related
[635]
Rausch Osthoff AK, Niedermann K, Braun J et al.. “2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis.” Annals of the rheumatic diseases (2018). PMID: 29997112 ↗
L1GUIDELINECited in: History and Evolution of Treatment
[636]
Combe B, Landewe R, Daien CI et al.. “2016 update of the EULAR recommendations for the management of early arthritis.” Annals of the rheumatic diseases (2016). PMID: 27979873 ↗
L1GUIDELINECited in: History and Evolution of Treatment
[637]
Fraenkel L, Bathon JM, England BR et al.. “2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2021). PMID: 34101376 ↗
L1GUIDELINECited in: History and Evolution of Treatment
[638]
Goodman SM, Springer BD, Chen AF et al.. “2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.” Arthritis care & research (2022). PMID: 35718887 ↗
L1GUIDELINECited in: History and Evolution of Treatment, Special Populations, Pregnancy & Fertility
[639]
Singh JA, Saag KG, Bridges SL et al.. “2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.” Arthritis care & research (2015). PMID: 26545825 ↗
L1GUIDELINECited in: History and Evolution of Treatment
[640]
Teuwen MMH, van Weely SFE, Vliet Vlieland TPM et al.. “Effectiveness of longstanding exercise therapy compared with usual care for people with rheumatoid arthritis and severe functional limitations: a randomised controlled trial.” Annals of the rheumatic diseases (2024). PMID: 38171602 ↗
L1RCTCited in: History and Evolution of Treatment
[641]
Atchia I, Brown AK, Chitale S et al.. “Recommendations for rheumatology ultrasound training and practice in the UK.” Rheumatology (Oxford, England) (2021). PMID: 33167033 ↗
L5GUIDELINECited in: History and Evolution of Treatment
[642]
Hanauer SB, Feagan BG, Lichtenstein GR et al.. “Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial.” Lancet (London, England) (2002). PMID: 12047962 ↗
L1RCTCited in: History and Evolution of Treatment
[643]
Simkin PA. “Oral zinc sulphate in rheumatoid arthritis.” Lancet (London, England) (1976). PMID: 60622 ↗
L1RCTCited in: History and Evolution of Treatment
[644]
Bombardier C, Laine L, Reicin A et al.. “Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group.” The New England journal of medicine (2000). PMID: 11087881 ↗
L1RCTCited in: History and Evolution of Treatment
[645]
Silverman E, Mouy R, Spiegel L et al.. “Leflunomide or methotrexate for juvenile rheumatoid arthritis.” The New England journal of medicine (2005). PMID: 15843668 ↗
L1RCTCited in: History and Evolution of Treatment
[646]
Fleischmann R, Mysler E, Bessette L et al.. “Long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis: results through 3 years from the SELECT-COMPARE study.” RMD open (2022). PMID: 35121639 ↗
L1RCTCited in: History and Evolution of Treatment
[647]
Smolen JS, Trefler J, Racewicz A et al.. “Efficacy and safety of CT-P47 versus reference tocilizumab: 32-week results of a randomised, active-controlled, double-blind, phase III study in patients with rheumatoid arthritis, including 8 weeks of switching data from reference tocilizumab to CT-P47.” RMD open (2024). PMID: 39424404 ↗
L1RCTCited in: History and Evolution of Treatment
[648]
Buch MH, Aletaha D, Combe BG et al.. “Efficacy and safety of filgotinib in patients with rheumatoid arthritis: week 156 interim results from a long-term extension study.” RMD open (2024). PMID: 39455065 ↗
L2RCTCited in: History and Evolution of Treatment
[649]
Kim HJ, Swan H, Kazmi SZ et al.. “Familial risk of seropositive rheumatoid arthritis and interaction with smoking: a population-based cohort study.” Rheumatology (Oxford, England) (2023). PMID: 36692153 ↗
L2COHORTCited in: History and Evolution of Treatment, Prevention, Screening & Surveillance
[650]
Van den Ende CH, Vliet Vlieland TP, Munneke M et al.. “WITHDRAWN: Dynamic exercise therapy for treating rheumatoid arthritis.” The Cochrane database of systematic reviews (2008). PMID: 18253972 ↗
L1SR_OBSCited in: History and Evolution of Treatment
[651]
Garner SE, Fidan DD, Frankish RR et al.. “Rofecoxib for rheumatoid arthritis.” The Cochrane database of systematic reviews (2005). PMID: 15674912 ↗
L1SR_OBSCited in: History and Evolution of Treatment
[652]
Radner H, Ramiro S, Buchbinder R et al.. “Pain management for inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and other spondylarthritis) and gastrointestinal or liver comorbidity.” The Cochrane database of systematic reviews (2012). PMID: 22258995 ↗
L1SR_OBSCited in: History and Evolution of Treatment
[653]
Alfadhli AA, McDonald JW, Feagan BG. “Methotrexate for induction of remission in refractory Crohn's disease.” The Cochrane database of systematic reviews (2005). PMID: 15674908 ↗
L1SR_OBSCited in: History and Evolution of Treatment
[654]
Alfadhli AA, McDonald JW, Feagan BG. “Methotrexate for induction of remission in refractory Crohn's disease.” The Cochrane database of systematic reviews (2003). PMID: 12535475 ↗
L1SR_OBSCited in: History and Evolution of Treatment
[655]
McDonald JW, Wang Y, Tsoulis DJ et al.. “Methotrexate for induction of remission in refractory Crohn's disease.” The Cochrane database of systematic reviews (2014). PMID: 25099640 ↗
L1SR_OBSCited in: History and Evolution of Treatment
[656]
Eccleston C, Cooper TE, Fisher E et al.. “Non-steroidal anti-inflammatory drugs (NSAIDs) for chronic non-cancer pain in children and adolescents.” The Cochrane database of systematic reviews (2017). PMID: 28770976 ↗
L1SR_OBSCited in: History and Evolution of Treatment
[657]
McDonald JW, Tsoulis DJ, Macdonald JK et al.. “Methotrexate for induction of remission in refractory Crohn's disease.” The Cochrane database of systematic reviews (2012). PMID: 23235598 ↗
L1SR_OBSCited in: History and Evolution of Treatment
[658]
Whittle SL, Hughes RA. “Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review.” Rheumatology (Oxford, England) (2004). PMID: 14963199 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
[659]
Huber LC, Distler O, Tarner I et al.. “Synovial fibroblasts: key players in rheumatoid arthritis.” Rheumatology (Oxford, England) (2006). PMID: 16567358 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
[660]
Choy E, Aletaha D, Behrens F et al.. “Monotherapy with biologic disease-modifying anti-rheumatic drugs in rheumatoid arthritis.” Rheumatology (Oxford, England) (2017). PMID: 27550301 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
[661]
Walker JG, Littlejohn GO, McMurray NE et al.. “Stress system response and rheumatoid arthritis: a multilevel approach.” Rheumatology (Oxford, England) (1999). PMID: 10556255 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
[662]
Dayer JM. “The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis.” Rheumatology (Oxford, England) (2003). PMID: 12817089 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
[663]
Choy EH, De Benedetti F, Takeuchi T et al.. “Translating IL-6 biology into effective treatments.” Nature reviews. Rheumatology (2020). PMID: 32327746 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
[664]
Scher JU, Abramson SB. “The microbiome and rheumatoid arthritis.” Nature reviews. Rheumatology (2011). PMID: 21862983 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
[665]
Chang MH, Fuhlbrigge RC, Nigrovic PA. “Joint-specific memory, resident memory T cells and the rolling window of opportunity in arthritis.” Nature reviews. Rheumatology (2024). PMID: 38600215 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
[666]
Semb AG, Ikdahl E, Wibetoe G et al.. “Atherosclerotic cardiovascular disease prevention in rheumatoid arthritis.” Nature reviews. Rheumatology (2020). PMID: 32494054 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
[667]
Frisell T, Saevarsdottir S, Askling J. “Family history of rheumatoid arthritis: an old concept with new developments.” Nature reviews. Rheumatology (2016). PMID: 27098907 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
[668]
Atzeni F, Rodríguez-Carrio J, Popa CD et al.. “Cardiovascular effects of approved drugs for rheumatoid arthritis.” Nature reviews. Rheumatology (2021). PMID: 33833437 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
[669]
Dutt S, Roul P, Yang Y et al.. “Multimorbidity Patterns and Rheumatoid Arthritis Disease Outcomes: Findings From a Multicenter, Prospective Cohort.” Arthritis care & research (2023). PMID: 37394710 ↗
L2OTHERCited in: History and Evolution of Treatment
[670]
Wang H, Chen H, Li Y et al.. “Mechanistic study on the reduction of TNF-α and β-CTX levels in RA patients by moxibustion combined with western medication through regulation of the Wnt/β-catenin pathway.” Frontiers in immunology (2026). PMID: 42254021 ↗
L1RCTCited in: History and Evolution of Treatment
[671]
Portal PHG, Peixoto GN, de Matos MR et al.. “Add-on tocilizumab versus placebo for resistant major depression in psychiatric outpatients with low-grade inflammation in a tertiary public hospital in Southern Brazil: randomised triple-blind clinical trial protocol.” BMJ open (2026). PMID: 42285573 ↗
L5TRIAL_NONRANDOMCited in: History and Evolution of Treatment
[672]
Yoshida Y, Hosokawa Y, Taogoshi T et al.. “Effect of different folic acid doses on methotrexate-related toxicity and its association with erythrocyte methotrexate-polyglutamates in patients with rheumatic diseases: a single-center exploratory randomized controlled trial.” Clinical rheumatology (2026). PMID: 42249242 ↗
L1RCTCited in: History and Evolution of Treatment
[673]
Masoud I, Al Shaer NSH, Masoud A et al.. “Antibody-Drug Conjugates in Solid Tumor Oncology and the Frontier of Precision Immunosuppression: A Mechanistic, Translational, and Clinical Review.” International journal of molecular sciences (2026). PMID: 42352921 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
[674]
Goodman SM, Springer BD, Chen AF et al.. “2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.” Arthritis & rheumatology (Hoboken, N.J.) (2022). PMID: 35722708 ↗
L1GUIDELINECited in: Special Populations, Pregnancy & Fertility
[675]
Goodman SM, Springer B, Guyatt G et al.. “2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.” Arthritis & rheumatology (Hoboken, N.J.) (2017). PMID: 28620948 ↗
L1GUIDELINECited in: Special Populations, Pregnancy & Fertility
[676]
Schanberg LE, Mulugeta LY, Akinlade B et al.. “Therapeutic Development in Polyarticular Course Juvenile Idiopathic Arthritis: Extrapolation, Dose Selection, and Clinical Trial Design.” Arthritis & rheumatology (Hoboken, N.J.) (2023). PMID: 37067688 ↗
L5TRIAL_NONRANDOMCited in: Special Populations, Pregnancy & Fertility
[677]
Fleischmann R, Baumgartner SW, Weisman MH et al.. “Long term safety of etanercept in elderly subjects with rheumatic diseases.” Annals of the rheumatic diseases (2005). PMID: 16150792 ↗
L2SR_OBSCited in: Special Populations, Pregnancy & Fertility
[678]
Vinet É, De Moura C, Pineau CA et al.. “Serious Infections in Rheumatoid Arthritis Offspring Exposed to Tumor Necrosis Factor Inhibitors: A Cohort Study.” Arthritis & rheumatology (Hoboken, N.J.) (2018). PMID: 29771477 ↗
L2COHORTCited in: Special Populations, Pregnancy & Fertility
[679]
Rom AL, Wu CS, Olsen J et al.. “Fetal growth and preterm birth in children exposed to maternal or paternal rheumatoid arthritis: a nationwide cohort study.” Arthritis & rheumatology (Hoboken, N.J.) (2014). PMID: 25393524 ↗
L2COHORTCited in: Special Populations, Pregnancy & Fertility
[680]
Tsao NW, Lynd LD, Sadatsafavi M et al.. “Patterns of Biologics Utilization and Discontinuation Before and During Pregnancy in Women With Autoimmune Diseases: A Population-Based Cohort Study.” Arthritis care & research (2018). PMID: 28973840 ↗
L2COHORTCited in: Special Populations, Pregnancy & Fertility
[681]
Köller MD, Aletaha D, Funovits J et al.. “Response of elderly patients with rheumatoid arthritis to methotrexate or TNF inhibitors compared with younger patients.” Rheumatology (Oxford, England) (2009). PMID: 19812228 ↗
L2SR_OBSCited in: Special Populations, Pregnancy & Fertility
[682]
Goodman SM, Menon I, Christos PJ et al.. “Management of perioperative tumour necrosis factor α inhibitors in rheumatoid arthritis patients undergoing arthroplasty: a systematic review and meta-analysis.” Rheumatology (Oxford, England) (2015). PMID: 26447162 ↗
L1SR_OBSCited in: Special Populations, Pregnancy & Fertility
[683]
Nguyen NV, Svenungsson E, Dominicus A et al.. “Hydroxychloroquine in lupus or rheumatoid arthritis pregnancy and risk of major congenital malformations: a population-based cohort study.” Rheumatology (Oxford, England) (2025). PMID: 38479815 ↗
L2COHORTCited in: Special Populations, Pregnancy & Fertility
[684]
Jinno S, Onishi A, Hattori S et al.. “Comparison of retention of biologics in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study.” Rheumatology (Oxford, England) (2025). PMID: 38317442 ↗
L2COHORTCited in: Special Populations, Pregnancy & Fertility
[685]
Nathan NO, Mørch LS, Wu CS et al.. “Rheumatoid arthritis and risk of spontaneous abortion: a Danish nationwide cohort study.” Rheumatology (Oxford, England) (2020). PMID: 31776579 ↗
L2COHORTCited in: Special Populations, Pregnancy & Fertility
[686]
Hiramatsu Y, Kotani T, Nakamura E et al.. “Effect of treat-to-target strategies on maternal and neonatal outcomes of rheumatoid arthritis: a multicentre real-world ANSWER cohort study.” Rheumatology (Oxford, England) (2026). PMID: 41134194 ↗
L2COHORTCited in: Special Populations, Pregnancy & Fertility
[687]
Salliot C, Nguyen Y, Gusto G et al.. “Female hormonal exposures and risk of rheumatoid arthritis in the French E3N-EPIC cohort study.” Rheumatology (Oxford, England) (2021). PMID: 33547777 ↗
L2COHORTCited in: Special Populations, Pregnancy & Fertility
[688]
Roodenrijs NMT, Hamar A, Kedves M et al.. “Pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of difficult-to-treat rheumatoid arthritis.” RMD open (2021). PMID: 33419871 ↗
L1SR_OBSCited in: Special Populations, Pregnancy & Fertility
[689]
Lien HJT, Pedersen TT, Jakobsen B et al.. “Single-cell resolution of longitudinal blood transcriptome profiles in rheumatoid arthritis, systemic lupus erythematosus and healthy control pregnancies.” Annals of the rheumatic diseases (2024). PMID: 38049980 ↗
L2OTHERCited in: Special Populations, Pregnancy & Fertility
[690]
Meissner Y, Fischer-Betz R, Andreoli L et al.. “EULAR recommendations for a core data set for pregnancy registries in rheumatology.” Annals of the rheumatic diseases (2020). PMID: 33055080 ↗
L5OTHERCited in: Special Populations, Pregnancy & Fertility
[691]
Brouwer J, Hazes JM, Laven JS et al.. “Fertility in women with rheumatoid arthritis: influence of disease activity and medication.” Annals of the rheumatic diseases (2014). PMID: 24833784 ↗
L2OTHERCited in: Special Populations, Pregnancy & Fertility
[692]
Visser K, Katchamart W, Loza E et al.. “Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative.” Annals of the rheumatic diseases (2008). PMID: 19033291 ↗
L1OTHERCited in: Special Populations, Pregnancy & Fertility
[693]
Camacho EM, Verstappen SM, Lunt M et al.. “Multiple adverse pregnancy outcomes before symptom onset are associated with a worse disease outcome in women with recent-onset inflammatory polyarthritis.” Annals of the rheumatic diseases (2011). PMID: 21998113 ↗
L2REVIEW_NARRATIVECited in: Special Populations, Pregnancy & Fertility
[694]
Ince-Askan H, Mandaviya PR, Felix JF et al.. “Altered DNA methylation in children born to mothers with rheumatoid arthritis during pregnancy.” Annals of the rheumatic diseases (2019). PMID: 31142478 ↗
L2OTHERCited in: Special Populations, Pregnancy & Fertility
[695]
Burmester GR, Landewé R, Genovese MC et al.. “Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis.” Annals of the rheumatic diseases (2016). PMID: 27338778 ↗
L2OTHERCited in: Special Populations, Pregnancy & Fertility
[696]
Ma KK, Nelson JL, Guthrie KA et al.. “Adverse pregnancy outcomes and risk of subsequent rheumatoid arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2014). PMID: 24574209 ↗
L3OTHERCited in: Special Populations, Pregnancy & Fertility
[697]
de Steenwinkel FD, Hokken-Koelega AC, de Ridder MA et al.. “Rheumatoid arthritis during pregnancy and postnatal catch-up growth in the offspring.” Arthritis & rheumatology (Hoboken, N.J.) (2014). PMID: 24578030 ↗
L2OTHERCited in: Special Populations, Pregnancy & Fertility
[698]
Chen JS, Roberts CL, Simpson JM et al.. “Pregnancy Outcomes in Women With Rare Autoimmune Diseases.” Arthritis & rheumatology (Hoboken, N.J.) (2015). PMID: 26434922 ↗
L2OTHERCited in: Special Populations, Pregnancy & Fertility
[699]
Zanetti A, Zambon A, Scirè CA et al.. “Impact of rheumatoid arthritis and methotrexate on pregnancy outcomes: retrospective cohort study of the Italian Society for Rheumatology.” RMD open (2022). PMID: 36597979 ↗
L2COHORTCited in: Special Populations, Pregnancy & Fertility
[700]
Secher AEP, Granath F, Glintborg B et al.. “Risk of pre-eclampsia and impact of disease activity and antirheumatic treatment in women with rheumatoid arthritis, axial spondylarthritis and psoriatic arthritis: a collaborative matched cohort study from Sweden and Denmark.” RMD open (2022). PMID: 36328400 ↗
L2COHORTCited in: Special Populations, Pregnancy & Fertility
[701]
Brouwer J, Fleurbaaij R, Hazes JMW et al.. “Subfertility in Women With Rheumatoid Arthritis and the Outcome of Fertility Assessments.” Arthritis care & research (2017). PMID: 27723275 ↗
L4OTHERCited in: Special Populations, Pregnancy & Fertility
[702]
Bortoluzzi A, Andreoli L, Carrara G et al.. “Improved Pregnancy Outcome in Patients With Rheumatoid Arthritis Who Followed an Ideal Clinical Pathway.” Arthritis care & research (2021). PMID: 31912644 ↗
L2OTHERCited in: Special Populations, Pregnancy & Fertility
[703]
Kuriya B, Hernández-Díaz S, Liu J et al.. “Patterns of medication use during pregnancy in rheumatoid arthritis.” Arthritis care & research (2011). PMID: 21557526 ↗
L2OTHERCited in: Special Populations, Pregnancy & Fertility
[704]
Quaak CH, Röder E, Wintjes HM et al.. “Time to pregnancy in women with rheumatoid arthritis who want to conceive treated according to a treat-to-target approach: a comparison of an observational cohort with a historical reference cohort.” The Lancet. Rheumatology (2026). PMID: 41905370 ↗
L2OTHERCited in: Special Populations, Pregnancy & Fertility
[705]
Boots AM, Maier AB, Stinissen P et al.. “The influence of ageing on the development and management of rheumatoid arthritis.” Nature reviews. Rheumatology (2013). PMID: 23774902 ↗
L5REVIEW_NARRATIVECited in: Special Populations, Pregnancy & Fertility
[706]
Østensen M, Förger F. “Management of RA medications in pregnant patients.” Nature reviews. Rheumatology (2009). PMID: 19506586 ↗
L5REVIEW_NARRATIVECited in: Special Populations, Pregnancy & Fertility
[707]
Takeuchi T, Kameda H. “The Japanese experience with biologic therapies for rheumatoid arthritis.” Nature reviews. Rheumatology (2010). PMID: 20877307 ↗
L5REVIEW_NARRATIVECited in: Special Populations, Pregnancy & Fertility
[708]
Akkara Veetil BM, Bongartz T. “Perioperative care for patients with rheumatic diseases.” Nature reviews. Rheumatology (2011). PMID: 22083219 ↗
L5REVIEW_NARRATIVECited in: Special Populations, Pregnancy & Fertility
[709]
Camellino D, Matteson EL, Buttgereit F et al.. “Monitoring and long-term management of giant cell arteritis and polymyalgia rheumatica.” Nature reviews. Rheumatology (2020). PMID: 32759996 ↗
L5REVIEW_NARRATIVECited in: Special Populations, Pregnancy & Fertility
[710]
Park J, Lim H, Choi S et al.. “Incidence and risk factors of postoperative infection after wrist arthroscopy: an 11-year nationwide population-based cohort study in South Korea.” Orthopaedics & traumatology, surgery & research : OTSR (2026). PMID: 42235885 ↗
L2COHORTCited in: Special Populations, Pregnancy & Fertility
[711]
Kajita Y, Harada Y, Takahashi R et al.. “Short- to mid-term clinical outcomes and survivorship of the Nexel total elbow arthroplasty in Japanese patients: a single-center retrospective study.” Journal of shoulder and elbow arthroplasty (2026). PMID: 42040741 ↗
L4COHORTCited in: Special Populations, Pregnancy & Fertility
[712]
Guan H, Zhou H, Yuan F et al.. “A retrospective cohort study in China: association between Tripterygium glycosides and reduced serum albumin levels in elderly rheumatoid arthritis patients.” Frontiers in medicine (2026). PMID: 41930137 ↗
L2COHORTCited in: Special Populations, Pregnancy & Fertility
[713]
Tanaka Y, Taylor PC, Ritsema JAS et al.. “Efficacy/Effectiveness, Safety and Treatment Persistence of Filgotinib in Rheumatoid Arthritis: A Narrative Review of Clinical Trials and Real-World Evidence.” Rheumatology and therapy (2026). PMID: 41903081 ↗
L5TRIAL_NONRANDOMCited in: Special Populations, Pregnancy & Fertility
[714]
Pina Vegas L, Drouin J, Weill A et al.. “Pregnancy outcomes in women with rheumatoid arthritis: an 11-year French nationwide study.” RMD open (2024). PMID: 38242551 ↗
L2OTHERCited in: Special Populations, Pregnancy & Fertility
[715]
Sigmo GD, Hauge S, Hetland HB et al.. “Men with psoriatic arthritis, rheumatoid arthritis and axial spondylarthritis have more children and at an earlier age than matched controls: results from a nationwide cohort.” RMD open (2025). PMID: 40789721 ↗
L2OTHERCited in: Special Populations, Pregnancy & Fertility
[716]
Alsing CL, Igland J, Nystad TW et al.. “Data-driven identification of subgroups in early rheumatoid arthritis: mortality and cardiovascular disease in a cohort from western Norway.” RMD open (2025). PMID: 41005975 ↗
L2OTHERCited in: Special Populations, Pregnancy & Fertility
[717]
Kumar C, Kuhn M, Herrmann K et al.. “Severe methotrexate toxicity in elderly patients under diuretics.” RMD open (2024). PMID: 38176739 ↗
L3OTHERCited in: Special Populations, Pregnancy & Fertility
[718]
Hamroun S, Martin de Frémont G, Costedoat-Chalumeau N et al.. “Evaluation of pregnancy outcomes in patients with rheumatoid arthritis compared with the general population: results from a French national prospective and matched study.” RMD open (2026). PMID: 42419787 ↗
L2OTHERCited in: Special Populations, Pregnancy & Fertility
[719]
Esperón P, Vital M, Giletti A. “The impact of gene polymorphisms on the response of methotrexate-based treatments.” European journal of clinical pharmacology (2026). PMID: 42104114 ↗
L5SR_OBSCited in: Special Populations, Pregnancy & Fertility
[720]
Yang M, Xu F, Zhang B et al.. “Age-stratified treatment response in rheumatoid arthritis: a systematic review, meta-analysis, and integrated genetic and single-cell evidence implicating IL6R/TYK2 signaling.” Clinical rheumatology (2026). PMID: 41845003 ↗
L1SR_OBSCited in: Special Populations, Pregnancy & Fertility
[721]
Schieir O, Tosevski C, Glazier RH et al.. “Incident myocardial infarction associated with major types of arthritis in the general population: a systematic review and meta-analysis.” Annals of the rheumatic diseases (2017). PMID: 28219882 ↗
L2SR_OBSCited in: Prevention, Screening & Surveillance
[722]
Jiang Y, Rudin RS, Solomon DH. “Clinical Visit Frequencies in Rheumatology: A Systematic Literature Review.” Arthritis care & research (2023). PMID: 36807719 ↗
L2SR_OBSCited in: Prevention, Screening & Surveillance
[723]
Björk M, Dragioti E, Alexandersson H et al.. “Inflammatory Arthritis and the Effect of Physical Activity on Quality of Life and Self-Reported Function: A Systematic Review and Meta-Analysis.” Arthritis care & research (2022). PMID: 34632707 ↗
L1SR_OBSCited in: Prevention, Screening & Surveillance
[724]
Rentsch CT, DeVito NJ, MacKenna B et al.. “Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform.” The Lancet. Rheumatology (2020). PMID: 33349815 ↗
L2COHORTCited in: Prevention, Screening & Surveillance
[725]
Feng J, Pan C, Gou Y et al.. “EAT-Lancet Diet Modifies the Risk of Rheumatoid Arthritis Through Metabolomic Signature.” Arthritis & rheumatology (Hoboken, N.J.) (2025). PMID: 40546003 ↗
L2OTHERCited in: Prevention, Screening & Surveillance
[726]
Takada H, Demoruelle MK, Deane KD et al.. “Expansion of HLA-DR Positive Peripheral Helper T and Naive B Cells in Anticitrullinated Protein Antibody-Positive Individuals At Risk for Rheumatoid Arthritis.” Arthritis & rheumatology (Hoboken, N.J.) (2024). PMID: 38412870 ↗
L3OTHERCited in: Prevention, Screening & Surveillance
[727]
Katz P, Pedro S, Michaud K. “Sleep Disorders Among Individuals With Rheumatoid Arthritis.” Arthritis care & research (2023). PMID: 35997482 ↗
L4OTHERCited in: Prevention, Screening & Surveillance
[728]
Klareskog L, Catrina AI, Paget S. “Rheumatoid arthritis.” Lancet (London, England) (2009). PMID: 19157532 ↗
L5OTHERCited in: Prevention, Screening & Surveillance
[729]
Hoving JL, Lacaille D, Urquhart DM et al.. “Non-pharmacological interventions for preventing job loss in workers with inflammatory arthritis.” The Cochrane database of systematic reviews (2014). PMID: 25375291 ↗
L1SR_OBSCited in: Prevention, Screening & Surveillance
[730]
Hu Y, Wen M, Wen L et al.. “Comorbid autoimmune disease in stiff-person syndrome spectrum disorder: a systematic review and meta-analysis.” Journal of neurology (2026). PMID: 42390536 ↗
L2SR_OBSCited in: Prevention, Screening & Surveillance
[731]
Panoulas VF, Metsios GS, Pace AV et al.. “Hypertension in rheumatoid arthritis.” Rheumatology (Oxford, England) (2008). PMID: 18467370 ↗
L5REVIEW_NARRATIVECited in: Prevention, Screening & Surveillance
[732]
Finckh A, Courvoisier D, Lamacchia C. “Measuring ACPA in the general population or primary care: is it useful?” RMD open (2020). PMID: 32079664 ↗
L5REVIEW_NARRATIVECited in: Prevention, Screening & Surveillance
[733]
Montes D, Hulshizer CA, Myasoedova E et al.. “Utilisation of cardiovascular preventive services in a rheumatoid arthritis population-based cohort.” RMD open (2023). PMID: 37945289 ↗
L2OTHERCited in: Prevention, Screening & Surveillance

Quick Reference

Overview and Recommendations

Background

Evaluation

Management

Board Review — High Yield

Deep Dive — Evidence Details

Definition, Classification & Nomenclature

Classification vs. Diagnosis

Disease Variants and Nomenclature

Pathophysiology & Mechanism

Epidemiology, Etiology & Risk Factors

Temporal Trends

Risk Factors

Special Populations

Clinical Presentation

Presenting Symptoms

Physical Examination Findings

Phenotypic Variants

Red Flags

Atypical Presentations

Diagnosis & Workup: Serology, Imaging, Synovial Fluid & Classification Criteria

Classification Criteria

Serology

Imaging

Synovial Fluid Analysis

Diagnostic Algorithm

Diagnostic Performance of Selected Autoantibodies

Severity, Disease Activity & Risk Stratification

Composite Disease Activity Indices

Risk Stratification for Treatment Decisions

Special Considerations in Disease Activity Assessment

Acute Management: Flares & Organ-Threatening Disease

Step 1: Confirm the Flare and Exclude Mimics

Step 2: First-Line Intervention, Short-Term Glucocorticoid Bridging

Step 3: Optimise Background DMARD Therapy

Step 4: Organ-Threatening Disease, RA-ILD and Vasculitis

Step 5: Resolution and Transition to Long-Term Management

Long-term Management: The DMARD Ladder & Treat-to-Target

Step 1: First-line Therapy, csDMARD + Short-term Glucocorticoids

Step 2: 3-6 Month Assessment, Stratify by Prognostic Factors

Step 3: Add bDMARD or tsDMARD

Step 4: Failure of First b/tsDMARD, Switch to Another Mechanism

Step 5: Tapering in Sustained Remission

Drug Comparison Table

Controversies and Guideline Disagreement

What NOT to Do

Immunosuppression Safety & Therapeutic Drug Monitoring

Pre-treatment Screening

Laboratory Monitoring

Therapeutic Drug Monitoring (TDM)

Infection Prevention

Retinopathy Screening

Perioperative Management

Multisystem & Extra-Articular Involvement (Organ-by-Organ Map)

Pulmonary involvement

Cardiovascular involvement

Ocular involvement

Hematologic involvement

Cutaneous and other systems

Complications: Disease-Driven & Treatment-Related

Disease-Driven Complications

Treatment-Related Complications

Controversies and Guideline Disagreement

History and Evolution of Treatment

Pre-biologic Era

Biologic Revolution

JAK Inhibitors

Safety Concerns

Treat-to-Target and Guidelines

Prevention

Non-pharmacologic

Special Populations, Pregnancy & Fertility

Pregnancy, Fertility, and Lactation

Pediatrics (Juvenile Idiopathic Arthritis)

Elderly-Onset Rheumatoid Arthritis

Immunocompromised Patients

Prevention, Screening & Surveillance

Cardiovascular Risk Screening

Step 5: Resolution and Transition to Long-Term

Perioperative

Screening