What is the recommended treatment for rheumatoid arthritis?

Treatment for Rheumatoid Arthritis

Start methotrexate immediately upon diagnosis at 15 mg weekly, titrate to 20-25 mg weekly, add short-term low-dose glucocorticoids (≤10 mg prednisone equivalent for <3 months) for bridging, and escalate to biologic DMARDs or JAK inhibitors if remission is not achieved within 6 months. 1

Immediate Treatment Upon Diagnosis

• Begin methotrexate as the anchor drug immediately at 15 mg weekly and titrate up to 20-25 mg weekly or maximum tolerated dose 1
• Methotrexate has greater efficacy and effectiveness than any other non-biologic DMARD, with comparable efficacy to biologic agents in DMARD-naïve patients 2
• Add short-term low-dose glucocorticoids (≤10 mg/day prednisone equivalent) for less than 3 months to provide rapid symptomatic relief while waiting for methotrexate to take effect 1, 3
• Administer methotrexate with food or milk; do not crush or divide tablets 4
• Supplement with folic acid to reduce toxicity 5

Alternative First-Line Agents

• For patients with contraindications to methotrexate, use leflunomide or sulfasalazine as alternative first-line agents 1

Treatment Goals and Monitoring Strategy

Target clinical remission (SDAI ≤3.3, CDAI ≤2.8) or at minimum low disease activity (SDAI ≤11, CDAI ≤10) as the primary goal 1, 3

• Monitor disease activity every 1-3 months during active disease using validated indices (SDAI, CDAI, inflammatory markers) 1, 3
• If no improvement within 3 months or target not reached by 6 months, adjust therapy immediately 1, 3
• Baseline assessment should include complete blood count with differential and platelet counts, hepatic enzymes, renal function tests, and chest X-ray 4
• During ongoing therapy, monitor hematology at least monthly and renal/liver function every 1-2 months 4

Treatment Escalation Algorithm

Step 1: Optimize Methotrexate Dosing

• Ensure methotrexate reaches 20-25 mg/week before declaring treatment failure 3
• This is a critical pitfall—underdosing methotrexate is a common error that leads to premature escalation 3

Step 2: Add Conventional DMARDs (Triple Therapy)

• If methotrexate optimization fails to achieve low disease activity, add sulfasalazine and hydroxychloroquine to create triple-DMARD therapy 3
• Hydroxychloroquine dosing for rheumatoid arthritis: 200-400 mg daily as single or divided doses 6

Step 3: Add Biologic DMARD or JAK Inhibitor

For patients with poor prognostic factors (autoantibodies, high disease activity, early erosions, or failure of two conventional DMARDs), add a biologic DMARD or JAK inhibitor to methotrexate 1

Biologic options include:

• TNF inhibitors 1
• IL-6 inhibitors (tocilizumab) 1, 3
• T-cell co-stimulation modulators (abatacept) 1, 3, 7
• B-cell depleting therapy (rituximab) 1, 3
• JAK inhibitors 1, 3

Management of Treatment Failure

Switching Biologics

• If the first biologic DMARD or JAK inhibitor fails, switch to a different mechanism of action rather than trying another drug from the same class 3
• This is critical: do not switch to another TNF inhibitor after TNF inhibitor failure 3
• After TNF inhibitor failure, consider tocilizumab (IL-6 receptor antagonist), abatacept (T-cell costimulation modulator), or rituximab (anti-CD20) 1, 3

Flare Management

Systemic Flares

• Administer short-term systemic glucocorticoids at ≤10 mg/day prednisone equivalent for less than 3 months 3
• Do not use long-term glucocorticoids (>1-2 years) as adverse effects (osteoporosis, cataracts, cardiovascular disease) outweigh benefits 3

Isolated Joint Flares

• Use intra-articular glucocorticoid injections for predominantly single-joint involvement 1, 3

Treatment Tapering in Remission

• In patients who achieve sustained remission, cautious tapering of DMARDs can be considered 1
• Taper biologics first, then reduce conventional DMARDs 1
• Complete drug-free remission is achievable in only 15-25% of patients; most will require ongoing DMARD therapy 1

Critical Pitfalls to Avoid

• Do not underdose methotrexate—must reach 20-25 mg/week before concluding inadequate response 3
• Do not use long-term glucocorticoids beyond 1-2 years due to serious adverse effects 3
• Do not switch within the same biologic class after first failure—change mechanism of action instead 3
• Do not write methotrexate prescriptions on a PRN basis—mistaken daily use of the weekly dose has led to fatal toxicity 4
• Caution with NSAIDs: concomitant administration with methotrexate may elevate and prolong serum methotrexate levels, though studies in rheumatoid arthritis patients typically include concurrent NSAID use at lower methotrexate doses (7.5-15 mg/week) without apparent problems 4