Methotrexate

Abstract

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Methotrexate (MTX) is a folate analogue originally developed in the 1940s as a highly selective inhibitor of dihydrofolate reductase (DHFR). Its use in the reduction of rheumatoid arthritis (RA) synovitis was first reported in a 1951 paper on six RA patients by Gubner and Ginsburg and explained as a cytotoxic effect on proliferating lymphocytes. Subsequently its efficacy in RA was proven in a series of papers in the mid 1980s and it is now the mainstay of RA therapy, both alone and in combination, as recommended in the guidelines of the American College of Rheumatology 2002 [1].