The use of methotrexate in rheumatoid arthritis

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Abstract

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.

Section snippets

Methods

A Medline search of published studies with key words “methotrexate,” “rheumatoid arthritis,” “DMARDs,” and “amethopterin” from 1950 to 2003 was conducted. From these studies and their accompanying references, a total of 1114 studies dating from 1952 to the present were reviewed and 131 were determined to be pertinent to our discussion. These manuscripts included a variety of subjects, including pharmacology, therapy of connective-tissue diseases, and use of DMARDs. The manuscripts were reviewed

Discussion

There is now a significant database on the efficacy of MTX in the treatment of RA. In addition, a large number of studies have shown the safety of MTX when prescribed correctly and with appropriate monitoring of patients. It is important to note that the ACR recommends that folate supplementation be considered in all patients taking MTX (76). (A clarification on the dosages suggested to be effective without interfering with efficacy can be found in a comment by Alarcón [128] and the reply by

Andrea T. Borchers, PhD: Visiting Postdoctoral Scholar, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA

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    Andrea T. Borchers, PhD: Visiting Postdoctoral Scholar, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA

    Carl L. Keen, PhD: Professor and Chair, Department of Nutrition, University of California at Davis, Davis, CA

    Gurtej S. Cheema, MD: Assistant Clinical Professor of Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA

    M. Eric Gershwin, MD: Professor of Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA.

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