Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis

J Rheumatol. 1989 Mar;16(3):313-20.


Forty-six patients with recalcitrant rheumatoid arthritis entered a trial encompassing a 2-week inpatient period plus a 16-week, randomized double blind, parallel study comparing placebo, 5 mg/m2 and 10 mg/m2 oral weekly methotrexate (MTX). An additional 6 patients, given 20 mg/m2 MTX, contributed to the toxicity, but not the efficacy analysis. All patients had "failed" either gold or D-penicillamine. A linear dose response relationship (placebo vs 5 mg/m2 vs 10 mg/m2) was found for 5 of 11 outcome variables: patient pain and patient global scale, physician global scale, joint tenderness count and activity of daily living scale (p less than 0.05 for each). Gastrointestinal toxicity (p = 0.002), dyspepsia (p less than 0.03) and stomatitis (p less than 0.09) occurred more commonly with MTX, and a general trend, although not significant, was found toward a dose toxicity relationship.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activities of Daily Living
  • Adult
  • Aged
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / rehabilitation
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Methotrexate / administration & dosage*
  • Middle Aged
  • Physical Therapy Modalities
  • Random Allocation


  • Methotrexate