What is the treatment of rheumatoid arthritis (RA)?

Treatment of Rheumatoid Arthritis

The optimal treatment approach for rheumatoid arthritis begins with methotrexate (15-25 mg weekly) as first-line therapy, with escalation to combination therapy or biologics if treatment targets are not met within 3-6 months. 1

Initial Treatment Strategy

• Methotrexate (MTX) is the cornerstone first-line disease-modifying antirheumatic drug (DMARD) for newly diagnosed RA, optimized to 20-25 mg weekly or maximum tolerated dose 1
• For patients with contraindications to MTX, alternative conventional synthetic DMARDs include hydroxychloroquine, sulfasalazine, or leflunomide 1
• Short-term glucocorticoids may be used during initial treatment or disease flares to rapidly control inflammation while waiting for DMARDs to take effect 1, 2
• Treatment targets should be established early, aiming for remission (SDAI ≤3.3, CDAI ≤2.8) or at minimum low disease activity (SDAI ≤11, CDAI ≤10) 2

Treatment Escalation Algorithm

At 3 Months Assessment:

• If high disease activity persists (SDAI >26 or CDAI >22) despite optimized MTX and prednisone, the probability of attaining remission at 1 year is low without treatment modification 2
• Options include:
  • Adding TNF inhibitors or abatacept (T-cell costimulation blocker) 2
  • Interleukin-1 receptor antagonist therapy (anakinra) is less effective and not recommended at this stage 2

At 6-12 Months Assessment:

• For persistent moderate disease activity (SDAI >11 to ≤26 or CDAI >10 to ≤22):
  • Add sulfasalazine and hydroxychloroquine to MTX (triple therapy) 2
  • Or switch to subcutaneous MTX for better bioavailability 2, 3
• For higher disease activity or inadequate response to the above:
  • Add/switch to TNF inhibitor 2
  • Add/switch to abatacept 2
  • Add anti-IL-6 receptor monoclonal antibody (tocilizumab) after inadequate TNF inhibitor response 2
  • Add anti-CD20 (rituximab) after inadequate TNF inhibitor response 2, 4

Beyond First Year of Treatment

• For patients with persistently moderate to high disease activity, increase MTX to 20-25 mg/week or maximum tolerated dose, with switch to subcutaneous administration if needed 2
• For patients on DMARD monotherapy with continued activity, add sulfasalazine and hydroxychloroquine to optimize MTX (triple therapy) 2
• For patients already on a biologic agent with inadequate response:
  • Either discontinue the biologic and initiate triple DMARD therapy 2
  • Or switch to an alternative biologic agent with a different mechanism of action 2
• Any new treatment should be tried for at least 3-6 months to fully assess efficacy 2

Biomarker-Guided Treatment Selection

• Presence of rheumatoid factor, anti-citrullinated protein antibodies, or elevated serum IgG predicts better response to rituximab 2, 1
• For seronegative patients with inadequate response to TNF inhibitors, consider abatacept or tocilizumab rather than rituximab 2

Treatment Tapering

• In patients achieving sustained remission for ≥1 year, consider cautious de-escalation of therapy 2, 1
• Approximately 15-25% of patients may achieve sustained drug-free remission 2
• Factors associated with successful tapering include shorter symptom duration, absence of rheumatoid factor or anti-citrullinated protein antibodies, lower disease activity before remission, and less baseline disability 2

Common Pitfalls to Avoid

• Inadequate MTX dosing - optimal dosing is 20-25 mg weekly; lower doses may lead to treatment failure 1, 5
• Long-term glucocorticoid use beyond 1-2 years increases risk of cataracts, osteoporosis, and cardiovascular disease 2, 1
• Failure to switch to parenteral MTX when oral administration is ineffective - subcutaneous MTX has higher bioavailability 3
• Insufficient duration of treatment trial (less than 3-6 months) before concluding treatment failure 2
• Not escalating therapy when treatment targets are not met 1, 6
• Using interleukin-1 receptor antagonist (anakinra) as first-line biologic, as it is generally less effective than other biologics 2