What is the recommended treatment for a patient with rheumatoid arthritis?

Rheumatoid Arthritis Treatment

Start methotrexate 15-25 mg weekly plus hydroxychloroquine 400 mg daily immediately upon diagnosis, add short-term low-dose glucocorticoids (≤10 mg prednisone daily for <3 months) for rapid symptom control, and escalate to biologic DMARDs if remission or low disease activity is not achieved within 6 months. 1, 2

Initial Treatment Strategy

First-Line Therapy

• Methotrexate is the anchor drug and should be initiated at 15-25 mg weekly with folic acid supplementation 1, 2, 3
• Rapidly escalate to the optimal dose of 25-30 mg weekly within a few weeks, maintaining this maximal dose for at least 3 months before declaring treatment failure 1, 2
• If oral methotrexate is not tolerated or inadequately absorbed, switch to subcutaneous administration 1, 2

Combination Therapy for Poor Prognostic Factors

• For patients with erosive disease, high rheumatoid factor/anti-CCP antibodies, or high disease activity, start combination therapy immediately 1, 2
• Add hydroxychloroquine 400 mg daily to methotrexate from the start 2, 4
• Consider adding sulfasalazine for complete triple therapy (methotrexate + hydroxychloroquine + sulfasalazine), which is more effective than methotrexate alone 1, 2, 5

Glucocorticoid Bridge Therapy

• Add low-dose glucocorticoids (≤10 mg/day prednisone equivalent) for rapid symptom control while DMARDs take effect 1, 2
• Use the lowest possible dose for the shortest duration (less than 3 months) 1, 2
• Critical pitfall: After 1-2 years, long-term corticosteroid risks (cataracts, osteoporosis, fractures, cardiovascular disease) outweigh benefits 1, 2, 6

Treatment Targets and Monitoring

Disease Activity Goals

• Primary target: Clinical remission (SDAI ≤3.3 or CDAI ≤2.8, or ACR-EULAR Boolean criteria) 1, 2
• Acceptable alternative: Low disease activity (SDAI ≤11 or CDAI ≤10) 1, 2

Monitoring Schedule

• Assess disease activity every 1-3 months during active disease using standardized measures 1, 2
• Aim for >50% improvement within 3 months 1, 2
• Target must be attained within 6 months 1, 2
• If no improvement by 3 months or target not reached by 6 months, therapy must be adjusted 1, 2

Escalation Strategy for Inadequate Response

When to Escalate

• Do not underdose methotrexate: Must reach 20-25 mg/week before concluding inadequate response 2, 6
• If <50% improvement at 3 months or target not reached at 6 months, escalate therapy 1, 2

Escalation Options for Patients with Poor Prognostic Factors

• Add a biologic DMARD or JAK inhibitor to methotrexate 1, 2
• First-line biologic options include:
  • TNF inhibitors (adalimumab 40 mg every other week, etanercept, infliximab) 1, 7
  • Non-TNF biologics (abatacept, tocilizumab) 1
  • JAK inhibitors (baricitinib) 1

Escalation Options for Patients Without Poor Prognostic Factors

• Add sulfasalazine and hydroxychloroquine to methotrexate (triple therapy) 1, 2
• Switch to subcutaneous methotrexate if not already done 1, 2
• If triple therapy fails, proceed to biologic DMARDs 1

Subsequent Biologic Failures

• Switch to another biologic DMARD with a different mechanism of action 1, 2
• After TNF inhibitor failure, consider rituximab, tocilizumab, or abatacept 1
• Allow 3-6 months to fully assess efficacy of any new treatment 1, 2

Special Considerations

Comorbidities Affecting Treatment Choice

• NYHA class III or IV heart failure: Use non-TNF inhibitor biologic or JAK inhibitor instead of TNF inhibitor 1
• Previous lymphoproliferative disorder: Rituximab is preferred over other DMARDs 1
• Hepatitis B surface antigen positive: Strongly recommend prophylactic antiviral therapy when initiating any biologic DMARD or JAK inhibitor 1
• Hepatitis B core antibody positive initiating rituximab: Strongly recommend prophylactic antiviral therapy regardless of surface antigen status 1

De-escalation in Sustained Remission

• Taper and discontinue prednisone once remission is achieved 1, 2
• After sustained remission ≥1 year, consider de-escalation of DMARD therapy 1, 2
• 15-25% of patients can achieve sustained drug-free remission 2

Critical Pitfalls to Avoid

• Never delay DMARD initiation: This leads to irreversible joint damage 1, 2, 3
• Never use NSAIDs or corticosteroids alone: These provide only symptomatic relief without disease modification 2
• Never undertreate with suboptimal methotrexate doses (<25 mg weekly): This prevents achieving treatment targets 2
• Never continue ineffective therapy beyond 6 months: Escalate if target not reached 1, 2, 6
• Never continue long-term corticosteroids beyond 1-2 years: Risks outweigh benefits 1, 2, 6