The pharmacogenetics of methotrexate

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.