What is Rheumatoid Arthritis?
Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune inflammatory joint disease characterised by symmetric polyarthritis (predominantly small joints of hands and feet), synovial inflammation, progressive joint destruction, and extra-articular manifestations (serositis, interstitial lung disease, vasculitis, nodules). Serological markers include anti-CCP antibodies (highest specificity) and rheumatoid factor.
Pathophysiology
RA is driven by dysregulated adaptive immunity — autoantigen presentation by APCs, T-cell activation, B-cell differentiation, and production of autoantibodies (RF, anti-CCP). TNF-α, IL-6, IL-1, and IL-17 drive synovial inflammation and activate osteoclasts, causing cartilage degradation and bone erosion. JAK-STAT signalling is a key intracellular pathway amplifying cytokine responses, providing the rationale for JAK inhibitor therapy.
Clinical Features & Symptoms
- Symmetric joint pain and swelling (MCP, PIP, wrist, MTP joints)
- Morning stiffness >1 hour (hallmark)
- Joint warmth and erythema
- Fatigue and constitutional symptoms
- Rheumatoid nodules (elbows, sacrum)
- Extra-articular: pleuritis, pericarditis, ILD, scleritis
- Cervical spine instability (atlanto-axial subluxation — check pre-operatively)
Diagnosis
2010 ACR/EULAR classification criteria (score ≥6 of 10): joint involvement (0–5), serology — RF/anti-CCP (0–3), acute phase reactants — CRP/ESR (0–1), symptom duration (0–1). Investigations: RF, anti-CCP, CRP, ESR, FBC, renal/liver function, CXR, hands/feet X-rays. Baseline DAS28 score for monitoring.
Current Treatment Guidelines
Treat-to-target (T2T)
Class I, Level A (EULAR)Target DAS28 remission (DAS28-CRP <2.6) or low disease activity (DAS28 <3.2). Reassess monthly, adjust therapy every 3 months if target not achieved. Clinical remission preferred over low disease activity when achievable.
Methotrexate (MTX) first-line
Class I, Level AOral or subcutaneous MTX 15–25 mg/week + folic acid 5 mg/week. Anchor therapy — most evidence-based csDMARD. If contraindicated: leflunomide or sulfasalazine ± hydroxychloroquine. Assess response at 3 months.
Add bDMARD if csDMARD fails
Class I, Level AAdd TNF inhibitor (adalimumab, etanercept, certolizumab) or IL-6 inhibitor (tocilizumab, sarilumab) or abatacept (T-cell co-stimulation blockade) after ≥3 months inadequate response to MTX. All equally effective; choice guided by comorbidities and preference.
JAK inhibitors (tofacitinib, baricitinib, upadacitinib)
Class IIa (with caution, updated 2022)Oral JAK inhibitors as alternative to bDMARDs after MTX failure. EULAR 2022 update: use with caution in patients ≥65, smokers, cardiovascular risk factors, malignancy history, or thromboembolic risk — due to ORAL Surveillance trial data showing increased MACE and malignancy vs TNFi.
Glucocorticoids (bridging)
Class IIa, Level BLow-dose prednisolone (≤7.5 mg/day) or short-course taper as bridging therapy during initiation/switch of csDMARDs or bDMARDs. Not recommended as long-term monotherapy. Taper and discontinue once DMARD takes effect.
Monitoring & Treatment Targets
DAS28 monthly until remission, then every 3–6 months. Full blood count and LFTs every 8–12 weeks on methotrexate. Annual cardiovascular risk assessment. Ophthalmology review if hydroxychloroquine >5 mg/kg/day. DEXA scan if on glucocorticoids >3 months.
Key Clinical Trials
Clinical Guidelines
External Resources
AI Clinical Analysis
Requires free account
Ask Prognia AI about Rheumatoid Arthritis — get evidence-graded answers from PubMed, the linked guidelines, and real clinical cases simultaneously.
Frequently Asked Questions
What is the first-line treatment for rheumatoid arthritis?
EULAR 2022 recommends methotrexate (MTX) as the anchor csDMARD for all newly diagnosed RA unless contraindicated. Start at 7.5–10 mg/week and escalate to 15–25 mg/week over 4–8 weeks. Always co-prescribe folic acid 5 mg/week to reduce mucositis and hepatotoxicity. Assess response at 3 months — if DAS28 target not achieved, add or switch DMARD.
When should biologic DMARDs be started in rheumatoid arthritis?
Biologic DMARDs (TNF inhibitors, IL-6 inhibitors, abatacept) are recommended when the DAS28 treatment target is not achieved after ≥3 months of conventional DMARD therapy (typically methotrexate ± combination). All bDMARDs have similar efficacy; choice depends on comorbidities, patient preference, route of administration, and cost.
Medical disclaimer: This content is intended for qualified healthcare professionals and does not constitute medical advice. Always apply clinical judgment and refer to current local guidelines and institutional protocols.