Rheumatoid Arthritis Treatment
Start methotrexate immediately as first-line therapy at 20-25 mg weekly (or maximum tolerated dose) as soon as rheumatoid arthritis is diagnosed, combined with short-term low-dose glucocorticoids that should be tapered within 1-2 years. 1, 2
Initial Treatment Strategy
Methotrexate is the anchor DMARD for newly diagnosed RA and should be part of the first treatment strategy for all patients with active disease. 1, 2 The optimal dose is 20-25 mg weekly, which can be given orally or subcutaneously with folic acid supplementation. 2, 3
For patients with contraindications or intolerance to methotrexate, alternative first-line conventional synthetic DMARDs include: 1, 2
- Leflunomide
- Sulfasalazine
- Hydroxychloroquine
Short-term glucocorticoids (low to moderately high doses) should be added to initial DMARD therapy to rapidly control inflammation, but must be tapered as quickly as clinically feasible and discontinued within 1-2 years to avoid serious adverse effects including cataracts, osteoporosis, and cardiovascular disease. 1, 2
Treatment Target and Monitoring
The treatment goal is remission or low disease activity, assessed using validated measures such as SDAI or CDAI. 1, 2
Reassess disease activity every 1-3 months and escalate therapy if the target is not achieved. 1 This "treat-to-target" approach with tight control monitoring is more important than the specific drug chosen and represents the cornerstone of modern RA management. 4
Escalation for Inadequate Response to Methotrexate Monotherapy
If methotrexate monotherapy fails after 3 months at optimal dosing: 1, 2
Option 1 - Triple DMARD Therapy: Add sulfasalazine and hydroxychloroquine to methotrexate (triple therapy). 1, 2 This combination is highly effective and less expensive than biologics. 4
Option 2 - Add a Biologic or Targeted Synthetic DMARD: For patients with poor prognostic features (positive rheumatoid factor or anti-CCP antibodies, bony erosions, extra-articular disease, functional limitation), add a biologic DMARD to methotrexate: 1, 2
First-Line Biologic Options:
- TNF inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab) combined with methotrexate 1, 2, 5
- IL-6 receptor antagonists (tocilizumab, sarilumab) - effective as monotherapy or with methotrexate 2, 6
- JAK inhibitors (tofacitinib, baricitinib) 1, 2
When First Biologic Fails
If a TNF inhibitor fails after 3 months: 1, 2
Option 1: Switch to a different TNF inhibitor (50-70% response rate) 2
Option 2: Switch to a non-TNF biologic with different mechanism: 1, 2
- Abatacept (T-cell costimulation modulator)
- Rituximab (anti-CD20 antibody) - particularly effective in seropositive patients with elevated rheumatoid factor, anti-CCP antibodies, or IgG 2
- Tocilizumab (IL-6 receptor antagonist) 1, 6
- JAK inhibitors 1, 2
Seronegative patients may respond better to abatacept or tocilizumab rather than rituximab. 2
Special Populations Requiring Modified Approach
Before starting biologic therapy, mandatory screening includes: 1, 5, 6
- Tuberculosis testing (except in COVID-19 patients on tocilizumab) - treat latent TB before initiating biologics 5, 6
- Hepatitis B and C screening 1
Exercise extreme caution or avoid biologics in patients with: 1, 5, 6
- Active or chronic infections
- Congestive heart failure
- History of malignancy (particularly lymphoproliferative disorders)
- Nontuberculous mycobacterial lung disease
Treatment De-escalation
For patients achieving sustained remission (typically 6-12 months), consider cautious tapering of therapy. 2 Approximately 15-25% of patients may achieve sustained drug-free remission, particularly those with: 2
- 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
Delaying DMARD initiation leads to irreversible joint damage and worse long-term outcomes - start treatment immediately upon diagnosis. 1, 3
Inadequate methotrexate dosing (using <20 mg weekly) or insufficient trial duration (<3 months at optimal dose) before declaring treatment failure. 2, 3
Prolonged glucocorticoid use beyond 1-2 years without appropriate monitoring and tapering increases risks of serious adverse effects. 2
Failure to escalate therapy when treatment targets are not met at 3-month reassessment intervals. 1, 2
Overlooking mandatory screening for tuberculosis and hepatitis before starting biologics, which can lead to life-threatening reactivation of latent infections. 1, 5, 6
Using biologics in combination with other biologics increases infection risk without proven additional benefit - avoid this practice. 6