What is the initial treatment for rheumatoid arthritis?

Initial Treatment for Rheumatoid Arthritis

Methotrexate (MTX) monotherapy at a starting dose of 15 mg/week with folic acid 1 mg/day is the recommended initial treatment for most patients with rheumatoid arthritis. 1, 2

First-Line Treatment Algorithm

• Start MTX at 15 mg/week orally with folic acid 1 mg/day as the initial therapy for most patients unless contraindicated 1
• Lower doses may be required in elderly patients and those with chronic kidney disease 1, 2
• Consider adding low-dose oral prednisone (5-10 mg/day) as a bridging therapy, starting with a moderate dose and tapering to 5 mg/day by week 8 1
• Folic acid supplementation should always be given with MTX to reduce toxicity without affecting efficacy 3, 4

Dose Optimization and Monitoring

• Rapidly escalate MTX dose if inadequate response occurs, with increments of 2.5-5 mg every 1-2 weeks up to 20-25 mg/week within 8 weeks 1, 2, 5
• Monitor disease activity every 1-3 months until treatment target is reached 1, 2
• Mandatory monitoring includes full blood cell count, serum transaminases, and creatinine at least monthly for the first 3 months, then every 1-3 months 2, 4
• The 3-month mark is a critical time point to assess response and determine if treatment modification is needed 1

Alternative Administration Routes

• Consider switching to subcutaneous MTX if:
  • Oral route is not effective enough
  • Gastrointestinal side effects occur
  • Required doses exceed 20 mg/week
  • Patient has poor compliance 2, 5
• Subcutaneous administration may provide better bioavailability, especially at higher doses 6, 5

Treatment Escalation for Inadequate Response

• If low disease activity is not achieved by 3 months with optimized MTX (20-25 mg/week), consider treatment modification 1
• Options for escalation at 3-6 months include:
  • Adding sulfasalazine and hydroxychloroquine for triple DMARD therapy
  • Adding a biologic agent (TNF inhibitor or abatacept) 1, 2
• The choice between triple therapy and biologic therapy should consider disease severity, cost, and patient factors 1

Non-Pharmacological Interventions

• Include dynamic exercises and occupational therapy as adjuncts to pharmaceutical treatment 1, 2
• Provide patient education about disease management and joint protection 1, 2
• Consider cognitive behavioral therapy for patients with fatigue 1

Important Considerations and Pitfalls

• Practical and cost considerations favor initial MTX monotherapy over combinations of DMARDs or biologic agents 1
• The TEAR trial showed no advantage of initial combination therapy with etanercept over MTX monotherapy with step-up therapy at 6 months 1
• Attaining minimal disease activity by 1 year is crucial, as patients who do not achieve remission by this time experience higher rates of joint erosion over the following decade 1
• The likely response to MTX cannot be reliably predicted based on current clinical assessments, necessitating close monitoring and dose adjustment 1
• Failure to supplement with folic acid can lead to unnecessary toxicity including cytopenias, gastrointestinal intolerance, and liver disease 3, 4