Methotrexate twice weekly vs once weekly in rheumatoid arthritis: a pilot double-blind, controlled study

Rheumatol Int. 2002 May;22(1):1-4. doi: 10.1007/s00296-002-0186-y.


Methotrexate (MTX) is the most commonly used disease-modifying antirheumatoid drug used in patients with rheumatoid arthritis. It is usually given on a weekly schedule, but as the half-life of its active compound, the polyglutamate MTX, is 3 days, we did a pilot study to see if MTX twice weekly is superior to MTX once weekly. Eighty patients with rheumatoid arthritis (RA) fulfilling the American College of Rheumatology (ACR) criteria were enrolled into a double-blind, controlled trial of 16-week duration. Patients achieving ACR scores of 20 and 50 were determined at 8 and 16 weeks. In addition, the incidence of hepatotoxicity was also studied. Of the 80 patients, 66 completed 8 weeks of study, whereas 53 completed 16 weeks of study. Most withdrawals were because of inefficacy. At 8 weeks, ACR 20 response (24/34 in once weekly and 22/32 in twice weekly) and ACR 50 response (16/34 in once weekly and 16/32 in twice weekly) in both groups were similar. Even at 16 weeks, there was no significant difference in ACR 20 and ACR 50 responses. Intent-to-treat analysis also yielded similar results. Five patients in each group had a mild reversible rise in transaminases. Our study suggests that MTX twice weekly has no advantage over once weekly regarding efficacy, and thus the currently used once weekly regimen is good enough till alternate dosing schedules are evaluated in a large multicentric trial.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / adverse effects
  • Arthralgia / drug therapy
  • Arthralgia / physiopathology
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Methotrexate / administration & dosage*
  • Methotrexate / adverse effects
  • Pain Measurement / drug effects
  • Pilot Projects
  • Treatment Outcome


  • Antirheumatic Agents
  • Methotrexate