The Methotrexate Story: How did a Cancer Chemotherapeutic Agent Become a Disease-modifying Antirheumatic Drug

Abstract

Abstract Weekly mini-pulse of low-dose methotrexate (LD-MTX) is presently the first-line conventional synthetic disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA) and several other systemic immunoinflammatory rheumatic diseases (SIRDs). Yet, most of the younger generation of rheumatologists around the world may be unaware of the interesting journey of MTX, from being an antifolate agent for use as cancer chemotherapy to becoming the mainstay of treatment for inflammatory arthritides and other SIRDs. This short essay narrates the journey of MTX from its precursor analog aminopterin to treat childhood leukemia, its name change from aminopterin to MTX, which became one of the major chemotherapeutic agents in oncology and then evolving as the mainstay of drug treatment for RA and other SIRDs. The seminal role of Gubner et al. from New York in 1953 in recognizing its steroid-sparing property in inflammatory diseases at doses much lower than that needed to treat cancer is highlighted.