The use of methotrexate in rheumatoid arthritis

Andrea T. Borchers, Carl L Keen, Gurtej S. Cheema, M. Eric Gershwin

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


Objective To address the long-term efficacy and toxicity issues related to methotrexate (MTX) and compare it with other disease-modifying antirheumatic drugs (DMARDs). Methods Review of the international literature on the clinical use of MTX in rheumatoid arthritis (RA) disease. Results MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival. The toxicity profile of MTX is well established and includes serious and sometimes fatal liver disease, pneumonitis, and cytopenias. Hence, regular and careful monitoring of patients taking MTX is essential, particularly when MTX is combined with other DMARDs. Folate supplementation can reduce some of the most common side effects of MTX, but it has not yet been established whether this translates into a reduced risk of serious disease. Another potential approach to reducing the toxicity of MTX is therapeutic drug monitoring and dose individualization. However, correlations between pharmacokinetics and clinical response have been addressed in only a few studies and with conflicting results. Conclusions MTX is an effective DMARD with a relatively safe profile compared with other therapies. Folate supplementation can significantly reduce the risk of MTX toxicity. Finally, it is essential that patients be monitored carefully to reduce the potential serious toxicities of MTX.

Original languageEnglish (US)
Pages (from-to)465-483
Number of pages19
JournalSeminars in Arthritis and Rheumatism
Issue number1
StatePublished - Aug 2004


  • Bone marrow suppression
  • liver toxicity
  • methotrexate
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Orthopedics and Sports Medicine
  • Rheumatology


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