What is the recommended treatment for rheumatoid arthritis?

Treatment Recommendations for Rheumatoid Arthritis

The recommended first-line treatment for rheumatoid arthritis is methotrexate (MTX) at 15-25 mg weekly, with the addition of low-dose glucocorticoids for initial disease control, followed by a treat-to-target approach with escalation to combination therapy or biologics if treatment targets are not met. 1

Initial Treatment Strategy

First-Line Therapy

• Start MTX at 10-15 mg/week (not less than 10 mg/week) 2
• Escalate MTX dose every 2-6 weeks up to 20-25 mg/week as tolerated 1, 2
• Consider adding low-dose glucocorticoids (≤10 mg/day prednisone equivalent) for the first 3-6 months as bridging therapy 1
• Prescribe folic acid supplementation (at least 5 mg weekly, taken at a distance from MTX dose) to reduce adverse effects 2, 3

For MTX Contraindications or Intolerance

• Use leflunomide or sulfasalazine as alternative first-line DMARDs 1

Monitoring and Treatment Targets

Monitoring Schedule

• Assess disease activity every 1-3 months in active disease 1
• Perform laboratory monitoring (CBC, liver function, renal function) monthly for first 3 months, then every 1-3 months 2

Treatment Targets

• Aim for remission or low disease activity in all patients 1
• If no improvement by 3 months or target not reached by 6 months, adjust therapy 1

Treatment Escalation Algorithm

Step 1: If Inadequate Response to MTX Monotherapy

For patients with low/moderate disease activity without poor prognostic factors:

• Consider adding hydroxychloroquine and sulfasalazine (triple therapy) 1
• OR switch to subcutaneous MTX if oral MTX is ineffective 1

For patients with high disease activity or poor prognostic factors:

• Add a biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD) 1
  • TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab)
  • OR abatacept (CTLA4-Ig)
  • OR IL-6 receptor antagonist (tocilizumab)
  • OR JAK inhibitors

Step 2: If Inadequate Response to First Biologic/Targeted Therapy

• Switch to a different biologic agent with the same or different mechanism of action 1
• For TNF inhibitor failures, consider switching to:
  • Another TNF inhibitor (up to 2 trials) 1
  • OR abatacept 1, 4
  • OR tocilizumab 1, 4
  • OR rituximab (especially in seropositive patients) 1
  • OR JAK inhibitor 1

Special Considerations

Serostatus Impact on Treatment Selection

• Rituximab may be more effective in seropositive patients (RF+, anti-CCP+) 1, 4
• Abatacept or tocilizumab may be preferred in seronegative patients who have failed TNF inhibitors 1, 4

Safety Considerations

• Screen for tuberculosis, hepatitis B/C before starting biologics 5
• Monitor for infections in patients on TNF inhibitors 5
• Use caution with JAK inhibitors in patients with cardiovascular risk factors 1

Tapering Considerations

• If sustained remission is achieved after tapering glucocorticoids, consider cautious tapering of biologics 1
• Only consider tapering conventional DMARDs after long-term sustained remission 1

Common Pitfalls to Avoid

• Underdosing MTX: Starting at doses below 10 mg/week is less effective 2
• Inadequate monitoring: Failure to assess response at 3-6 months may delay necessary treatment adjustments 1
• Omitting folic acid: Supplementation reduces MTX toxicity without compromising efficacy 3
• Premature switching: Allow adequate trial duration (3-6 months) before concluding treatment failure 1
• Neglecting treat-to-target approach: Failure to adjust therapy when targets aren't met leads to worse outcomes 1, 6

The evidence strongly supports a structured, step-up approach to RA treatment with regular monitoring and adjustment based on disease activity measures, prioritizing early intervention and a treat-to-target strategy to prevent joint damage and improve long-term outcomes.