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Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24.

The pharmacogenetics of methotrexate.

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  • 1Epidemiology Unit, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT UK.


Methotrexate (MTX) is a cornerstone of therapy for rheumatoid arthritis. However, it is not universally effective and up to one-third of patients fail to respond to treatment, either because of inefficacy or adverse events, although at present it is not possible to predict therapy response accurately. Pharmacogenetics is the study of variability in drug response due to heredity. MTX has a complex intracellular metabolism and acts via a number of key enzymes. This review critically appraises the studies of MTX pharmacogenetics and highlights the need for further work in this area.

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