What is the recommended initial treatment regimen for rheumatoid arthritis?

Treatment for Rheumatoid Arthritis

Immediate First-Line Therapy

Start methotrexate 15 mg orally once weekly with folic acid 1 mg daily immediately upon diagnosis, rapidly escalating to 25–30 mg weekly within 4–8 weeks to prevent irreversible joint damage. 1, 2

• Delaying disease-modifying antirheumatic drug (DMARD) initiation leads to permanent joint destruction that cannot be reversed—treatment must begin at the time of diagnosis. 1
• Methotrexate is the "anchor drug" for rheumatoid arthritis based on Level I evidence showing approximately one-third of patients have no radiographic progression after 12 months. 1
• If oral methotrexate at 20–25 mg weekly is poorly tolerated or ineffective after 3 months, switch to subcutaneous administration before declaring treatment failure, as parenteral bioavailability is superior. 1, 3, 4

Adjunctive Bridge Therapy

• Add low-dose prednisone ≤10 mg daily (or equivalent) for rapid symptom control while methotrexate takes effect, using the lowest dose for less than 3 months. 1, 2
• NSAIDs (e.g., celecoxib, ibuprofen) may be continued for additional symptomatic relief after evaluating cardiovascular and renal risks, but they provide zero disease-modifying benefit and do not prevent joint damage. 1, 5, 6
• Corticosteroids beyond 1–2 years cause cumulative toxicity (fractures, cataracts, cardiovascular disease) that outweighs any benefit. 1

Treatment Targets and Monitoring Schedule

The primary goal is clinical remission (SDAI ≤3.3 or CDAI ≤2.8), with low disease activity (SDAI ≤11 or CDAI ≤10) as an acceptable alternative. 1, 2

• Assess disease activity every 1–3 months using validated composite measures (SDAI, CDAI, or DAS28) until the target is reached. 1, 2
• Expect ≥50% improvement within the first 3 months of therapy; if this does not occur, escalate treatment immediately. 1
• The treatment target must be attained within 6 months—failure to reach this mandates escalation to combination DMARD or biologic therapy. 1, 2

Escalation Strategy for Inadequate Response

Patients Without Poor Prognostic Factors

• Add sulfasalazine 500 mg twice daily and hydroxychloroquine 200 mg twice daily to methotrexate (triple DMARD therapy) if inadequate response at 3 months. 1, 2
• Triple therapy yields 77% sustained improvement versus 33% with methotrexate alone. 1

Patients With Poor Prognostic Factors

Poor prognostic factors include high rheumatoid factor or anti-CCP titers, high baseline disease activity, early erosive changes on imaging, or failure of two conventional DMARDs. 1

• Add a TNF inhibitor (adalimumab, etanercept, infliximab, certolizumab, golimumab) to methotrexate as the preferred first-line biologic agent. 1, 6
• Alternative biologic classes include IL-6 receptor antagonists (tocilizumab), T-cell costimulation modulators (abatacept), or rituximab in selected cases. 1, 6
• JAK inhibitors (tofacitinib, baricitinib) are acceptable after biologic failure or when biologics are unsuitable. 1
• Biologic agents should be combined with methotrexate whenever possible because combination therapy demonstrates superior efficacy and reduces immunogenicity. 1, 5

After First Biologic Failure

• Switch to a biologic with a different mechanism of action if the initial TNF inhibitor fails. 1
• Allow 3–6 months to fully assess efficacy of any newly introduced therapy before making further changes. 1, 5

Critical Pitfalls to Avoid

• Never rely on NSAIDs or corticosteroids as sole therapy—this permits unchecked irreversible joint damage. 1, 5
• Never delay DMARD initiation waiting for positive serologies or elevated inflammatory markers—clinical synovitis (persistent joint swelling) is sufficient indication. 5
• Never continue ineffective therapy beyond 3 months without escalation—undertreating patients with suboptimal methotrexate doses (<25 mg weekly) prevents achieving treatment targets. 1, 5
• Never use high-dose corticosteroids as monotherapy—they do not halt radiographic progression and cause significant long-term toxicity. 1

Baseline Monitoring Before Methotrexate

• Obtain complete blood count, hepatic function tests (AST, ALT), renal function (creatinine, eGFR), and tuberculosis screening (TST or IGRA) before starting methotrexate. 1, 7
• Administer age-appropriate vaccines, including recombinant herpes zoster vaccine, at least 2–4 weeks before initiating any biologic DMARD. 1

Non-Pharmacologic Interventions

• Incorporate structured exercise programs (aerobic, resistance, aquatic, or mind-body exercise) to improve physical function and pain. 1
• Provide comprehensive occupational therapy for work modifications and patient education about disease management. 1, 2