What is the recommended treatment protocol for rheumatoid arthritis using Methotrexate (Disease-Modifying Antirheumatic Drug)?

Methotrexate Treatment Protocol for Rheumatoid Arthritis

For patients with rheumatoid arthritis, oral methotrexate should be initiated at 10-15 mg/week and titrated to at least 15 mg/week within 4-6 weeks, with folic acid supplementation of at least 5 mg/week to reduce toxicity. 1, 2

Initial Dosing and Route of Administration

• Oral methotrexate is conditionally recommended over subcutaneous methotrexate when initiating therapy due to ease of administration and similar bioavailability at typical starting doses 1
• Start with 10-15 mg/week orally, with escalation to at least 15 mg/week within 4-6 weeks 1, 2
• Further dose escalation up to 20-30 mg/week may provide additional efficacy depending on clinical response and tolerability 2, 3
• For patients with low disease activity, hydroxychloroquine is conditionally recommended over other conventional synthetic DMARDs (csDMARDs), and sulfasalazine is conditionally recommended over methotrexate 1
• For patients with moderate-to-high disease activity, methotrexate monotherapy is conditionally recommended over combination with biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) 1

Monitoring Protocol

• Before starting methotrexate, obtain: 2, 4

  • Complete blood count (CBC)
  • Liver function tests (ALT, AST, albumin)
  • Serum creatinine
  • Chest X-ray (within previous year)
  • Hepatitis B and C serologies (recommended)

• During treatment, monitor: 2, 4

  • ALT/AST, creatinine, and CBC every 1-1.5 months until stable dose
  • Then continue monitoring every 1-3 months
  • Clinical assessment for side effects at each visit

Management of Inadequate Response or Intolerance

• For patients not tolerating oral weekly methotrexate, consider these strategies before switching to alternative DMARDs: 1

  • Split dosing of oral methotrexate over 24 hours
  • Switching to subcutaneous administration
  • Increasing folic acid supplementation

• For patients with inadequate response to oral methotrexate at maximum tolerated dose: 1, 5

  • Switch to subcutaneous methotrexate before adding or switching to alternative DMARDs
  • Subcutaneous administration has greater bioavailability and may provide higher clinical efficacy 5, 6

Folic Acid Supplementation

• Prescribe at least 5 mg folic acid per week with methotrexate therapy 1, 2
• Folic acid supplementation reduces gastrointestinal and liver toxicity without reducing efficacy 1, 7
• Consider increasing folic acid dose if patient experiences side effects 1, 2

Special Considerations

• Methotrexate is appropriate for long-term use based on its acceptable safety profile 1
• Methotrexate can be safely continued during perioperative periods for patients undergoing elective orthopedic surgery 1
• Contraception is essential as methotrexate should not be used for at least 3 months before planned pregnancy for both men and women 1, 4
• Stop methotrexate if ALT/AST increases to greater than three times the upper limit of normal 1, 4

Common Pitfalls and Caveats

• Inadequate dosing is a common reason for treatment failure - ensure appropriate dose escalation to at least 15 mg/week 1, 2
• Premature switching to biologics without optimizing methotrexate dosing or route of administration may lead to unnecessary costs and risks 8, 5
• Failure to provide adequate folic acid supplementation increases risk of adverse effects 1, 2
• Oral bioavailability of methotrexate decreases at doses above 15 mg/week, potentially limiting efficacy compared to parenteral administration 5, 6
• Patient education about weekly (not daily) dosing is critical to prevent potentially fatal dosing errors 4