What is the recommended treatment for rheumatoid arthritis?

Rheumatoid Arthritis Treatment

Start methotrexate immediately as first-line therapy, optimized to 20-25 mg weekly, and escalate treatment every 3 months if moderate or high disease activity persists, with the goal of achieving remission or low disease activity. 1

Initial Treatment Strategy

Methotrexate is the cornerstone of RA treatment and should be initiated as soon as the diagnosis is made. 2, 1 The optimal dose is 20-25 mg weekly (oral or subcutaneous) with folic acid supplementation. 1, 3 This should not be delayed, as early aggressive therapy prevents irreversible joint damage and improves long-term outcomes. 3

For patients with contraindications or intolerance to methotrexate, alternative conventional synthetic DMARDs include: 2, 1

• Leflunomide
• Sulfasalazine
• Hydroxychloroquine

Short-term glucocorticoids (low to moderate doses) can be added during initial treatment to bridge symptom control while DMARDs take effect, but must be tapered rapidly and discontinued within 1-2 years to avoid serious adverse effects including cataracts, osteoporosis, and cardiovascular disease. 2, 1

Treatment Escalation Algorithm

Reassess disease activity every 3 months using validated measures (SDAI or CDAI). 2, 1 If the patient has not achieved low disease activity or remission, escalate therapy immediately according to the following algorithm:

For Patients with Moderate or High Disease Activity After 3 Months of Methotrexate:

If poor prognostic features are present (rheumatoid factor positive, anti-CCP antibodies positive, bony erosions, extra-articular disease, functional limitation): 2

• Add a biologic DMARD (TNF inhibitor preferred) combined with methotrexate 2, 1

If poor prognostic features are absent: 2

• Add combination conventional synthetic DMARD therapy: methotrexate + hydroxychloroquine + sulfasalazine (triple therapy), OR
• Switch to another conventional synthetic DMARD (leflunomide or sulfasalazine)

Biologic DMARD Selection

First-line biologic therapy should be a TNF inhibitor (adalimumab, certolizumab, etanercept, golimumab, or infliximab) combined with methotrexate. 2, 4 TNF inhibitors reduce signs and symptoms, inhibit structural damage progression, and improve physical function. 4

Alternative first-line biologics include tocilizumab (IL-6 receptor antagonist), which can be used as monotherapy or combined with methotrexate. 1, 5

If First TNF Inhibitor Fails After 3 Months:

Switch to either: 2, 1

• Another TNF inhibitor (50-70% response rate with second TNF inhibitor) 1
• Non-TNF biologic with different mechanism: abatacept (T-cell costimulation modulator), rituximab (anti-CD20), or tocilizumab (IL-6 receptor antagonist)

Biomarker-guided selection improves outcomes: 1

• Rituximab is preferred for patients who are rheumatoid factor positive or anti-CCP positive (predicts better response)
• Abatacept or tocilizumab may be preferred for seronegative patients

If Non-TNF Biologic Fails:

Reassess at 6 months (longer time to peak effect compared to TNF inhibitors). 2 If moderate or high disease activity persists, switch to another biologic with a different mechanism of action. 2, 1

JAK inhibitors (tofacitinib, baricitinib) are oral targeted synthetic DMARDs effective after TNF inhibitor failure. 1

Critical Safety Screening Before Biologics

Before initiating any biologic DMARD, mandatory screening includes: 2, 1, 4, 5

• Tuberculosis testing (TST or IGRA) regardless of risk factors—treat latent TB before starting biologics
• Hepatitis B and C screening—do not use biologics in untreated chronic hepatitis B
• Assessment for active infections, congestive heart failure (NYHA Class III-IV is contraindication), and history of malignancy

Patients on biologics have increased risk of serious infections including tuberculosis reactivation, invasive fungal infections, and opportunistic infections. 4, 5 Discontinue biologic immediately if serious infection develops. 4, 5

Special Populations Requiring Modified Approach

For patients with hepatitis, heart failure (NYHA Class III-IV), lymphoproliferative disorders, previous serious infections, or recent malignancy (within 5 years), biologic selection requires careful consideration: 1

• Rituximab may be preferred in patients with history of lymphoproliferative malignancy or previously treated solid malignancy 1
• TNF inhibitors are contraindicated in NYHA Class III-IV heart failure 4

Treatment Tapering in Sustained Remission

For patients achieving sustained remission (at least 6 months of low disease activity), consider cautious de-escalation of therapy. 1 Approximately 15-25% of patients may achieve sustained drug-free remission, particularly those with: 1

• Shorter symptom duration before treatment
• Absence of rheumatoid factor or anti-CCP antibodies
• Lower disease activity before achieving remission
• Less baseline disability

Critical Pitfalls to Avoid

Do not delay DMARD initiation—every month of delay increases risk of irreversible joint damage and worse long-term outcomes. 3

Do not use inadequate methotrexate dosing—doses below 20 mg weekly are often subtherapeutic; optimize to 20-25 mg weekly before declaring treatment failure. 1, 3

Do not continue ineffective therapy—if treatment target is not met after 3 months, escalate immediately rather than waiting. 2, 1, 6 The treat-to-target strategy with tight control monitoring is more important than the specific drug chosen. 6

Do not use long-term glucocorticoids without a clear tapering plan—prolonged use beyond 1-2 years causes serious adverse effects. 1

Do not use NSAIDs or celecoxib as primary RA therapy—these provide only symptomatic relief and do not prevent joint damage; they should never replace DMARDs. 7

Do not overlook mandatory TB and hepatitis screening before biologics—this prevents life-threatening reactivation of latent infections. 2, 1