What is the recommended treatment for Rheumatoid Arthritis (RA)?

Treatment of Rheumatoid Arthritis

Methotrexate (MTX) should be the first-line treatment for most patients with rheumatoid arthritis, starting at 10-15 mg/week with rapid escalation to 20-25 mg/week within 4-6 weeks, following a treat-to-target approach aimed at achieving low disease activity or remission. 1, 2

Initial Treatment Approach

Early RA (Disease Duration <6 Months)

• Start with MTX monotherapy for most patients with early RA 1
• Initial dosing:
  • Start at 10-15 mg/week 2, 3
  • Rapidly escalate to 20-25 mg/week within 4-6 weeks 2, 4
  • Consider subcutaneous administration for better bioavailability or if oral MTX causes intolerable side effects 2, 4
• Add folic acid supplementation (minimum 5 mg weekly, taken at a distance from MTX) to reduce adverse effects 2, 3

Established RA (Disease Duration ≥6 Months)

• Follow the same MTX approach as for early RA
• Use a targeted treatment approach with regular monitoring of disease activity using validated measures (DAS28, CDAI, SDAI) 1, 2
• Assess response within 3 months and aim to reach target within 6 months 2

Treatment Escalation Algorithm

If Inadequate Response to MTX Monotherapy After 3 Months:

1. First escalation step:

   • Consider switching from oral to subcutaneous MTX (maintain same dose) 2, 4
   • OR add short-term low-dose glucocorticoids (≤10 mg/day prednisone equivalent) as bridge therapy 1
   • OR add another conventional synthetic DMARD (csDMARD) such as hydroxychloroquine, sulfasalazine, or leflunomide 1

2. Second escalation step (if target not reached by 6 months):

   • For moderate-to-high disease activity: Add a biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD) 1
     • TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab pegol)
     • T-cell costimulation inhibitor (abatacept)
     • IL-6 receptor inhibitors (tocilizumab, sarilumab)
     • JAK inhibitors (tofacitinib, baricitinib, upadacitinib)
   • Continue MTX when adding biologics as combination therapy has superior efficacy 1, 5

3. Third escalation step (if inadequate response to first biologic):

   • Switch to a different mechanism of action:
     • After TNF inhibitor failure, consider rituximab (anti-CD20 antibody) in combination with MTX 1, 5
     • OR consider IL-6 receptor inhibitors or JAK inhibitors 1

Monitoring and Assessment

• Baseline assessments before starting MTX 2, 3:

  • Full blood count
  • Liver function tests (transaminases)
  • Kidney function (serum creatinine, creatinine clearance)
  • Chest radiograph
  • Hepatitis B and C serology
  • Serum albumin

• Regular monitoring during treatment 2, 3:

  • Full blood count, liver and kidney function tests monthly for first 3 months, then every 1-3 months
  • Disease activity assessment every 1-3 months in active disease using validated measures

Treatment Tapering

• Consider tapering medication only after sustained low disease activity or remission for at least 6 months 1
• When tapering, reduce dose gradually rather than discontinuing medication abruptly 1
• Biologic DMARDs can be tapered before conventional DMARDs 1

Common Pitfalls and Caveats

• Underdosing MTX: Many patients receive suboptimal doses. Ensure appropriate dose escalation to 20-25 mg/week unless limited by side effects 4
• Premature switching: Allow adequate time (3-6 months) for MTX to demonstrate full efficacy before concluding treatment failure 4
• Route of administration: Consider subcutaneous MTX for patients with inadequate response or intolerance to oral MTX due to better bioavailability 2, 4
• Glucocorticoid use: While effective for short-term symptom control, limit duration to <3 months due to long-term safety concerns 1
• Monitoring gaps: Ensure consistent monitoring of both disease activity and potential medication toxicity 2
• Folic acid omission: Always provide folic acid supplementation with MTX to reduce adverse effects 2, 3

By following this structured approach to RA treatment, focusing on early intervention with MTX and a treat-to-target strategy, patients have the best chance of achieving disease control, preventing joint damage, and maintaining quality of life.