What is the best treatment for rheumatoid arthritis?

Best Treatment Approach for Rheumatoid Arthritis

The most effective treatment approach for rheumatoid arthritis is a step-up strategy starting with methotrexate as first-line therapy, followed by triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) or biologic agents if inadequate response, with treatment decisions guided by disease activity measures. 1, 2

Initial Treatment Strategy

• Methotrexate should be the first-line disease-modifying antirheumatic drug (DMARD) for most patients with rheumatoid arthritis due to its established efficacy, safety profile, and cost-effectiveness 2, 3
• Start with a high initial dose of methotrexate followed by rapid titration to improve response, typically aiming for 15-25 mg weekly 4
• Consider subcutaneous methotrexate administration if oral methotrexate is not tolerated or for improved bioavailability at higher doses 3, 4
• Continue methotrexate for at least 3-6 months to fully assess efficacy, as long as some response is seen within the first 3 months 1, 5

Treatment Based on Disease Activity Assessment

• Use standardized disease activity measures like Simplified Disease Activity Index (SDAI) or Clinical Disease Activity Index (CDAI) to guide treatment decisions 1
• For patients with low disease activity (SDAI ≤11 or CDAI ≤10), continue current DMARD regimen 1, 6
• For patients with moderate to high disease activity (SDAI >11 or CDAI >10) despite methotrexate, escalate therapy 1

Treatment Escalation Options

Option 1: Triple Therapy

• Combination of methotrexate, sulfasalazine, and hydroxychloroquine (triple therapy) has shown excellent efficacy with probability of ACR50 response of 61% 2, 7
• Triple therapy is cost-effective and has a well-established safety profile 2, 7

Option 2: Biologic DMARDs

• TNF inhibitors (adalimumab, etanercept, infliximab, certolizumab) in combination with methotrexate are effective for patients with inadequate response to conventional DMARDs 1, 8, 9
• Non-TNF biologics like abatacept, tocilizumab, or rituximab are alternatives, particularly for patients who are seronegative for rheumatoid factor (consider abatacept or tocilizumab) or seropositive (rituximab may be more effective) 1, 5
• Adalimumab is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting structural damage progression, and improving physical function in patients with moderately to severely active rheumatoid arthritis 8

Monitoring and Adjustment

• Monitor disease activity every 1-3 months in active disease 5
• If no improvement after 3 months of any therapy, consider adjusting treatment 1, 5
• New treatments should typically be tried for 3-6 months to fully assess efficacy 1, 5

Important Considerations and Pitfalls

• Patients on biologic therapy require tuberculosis screening before initiation 8
• Risk of serious infections is increased with biologic agents, particularly when combined with other immunosuppressants 8
• After achieving sustained remission for ≥1 year, consider de-escalation of therapy 1, 6
• The maximal effect of treatment may not be seen before 6 months in many patients 5
• Biomarkers like rheumatoid factor positivity may help guide therapy selection (e.g., rituximab may be more effective in seropositive patients) 1

Special Situations

• For patients with significant comorbidities, carefully weigh benefits against risks of each therapy 5
• After the first 1-2 years, the benefits of long-term corticosteroid therapy are often outweighed by risks including cataracts, osteoporosis, fractures, and cardiovascular disease 1
• In patients with fibromyalgia and RA, composite disease activity measures may be misleadingly high due to tender joint counts and patient global assessment 1