Low-dose methotrexate in rheumatic diseases--efficacy, side effects, and risk factors for side effects

Semin Arthritis Rheum. 1994 Apr;23(5):310-27. doi: 10.1016/0049-0172(94)90027-2.


Controlled trials and observational studies have shown low-dose methotrexate (MTX) to be a second-line agent of high potency with a favorable profile of safety and tolerability in the treatment of rheumatoid arthritis (RA). Its risk-benefit ratio in psoriatic arthritis is less well documented. Preliminary reports on its beneficial effects in other disorders, including the systemic manifestations of RA, other spondyloarthritides, and collagen vascular diseases, merit more detailed examination. Gastrointestinal intolerance and hepatic enzyme elevation are the most frequent side effects of MTX; life-threatening events such as severe hemocytopenia and MTX pneumonitis are rare and amenable to prevention by recognizing risk factors and premonitory signs. Hepatotoxicity does not appear to be a major limiting factor in RA patients over the first 2 to 3 years of MTX therapy; its impact on long-term tolerance remains to be clarified.

Publication types

  • Review

MeSH terms

  • Arthritis, Rheumatoid / drug therapy*
  • Clinical Trials as Topic
  • Dose-Response Relationship, Drug
  • Humans
  • Liver Cirrhosis / epidemiology
  • Lung Diseases / epidemiology
  • Methotrexate* / administration & dosage
  • Methotrexate* / adverse effects
  • Methotrexate* / standards
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Vascular Diseases / epidemiology


  • Methotrexate