Off-Label Uses of Methotrexate

Methotrexate (MTX), originally developed as a chemotherapeutic agent, has evolved into a versatile immunomodulatory drug with extensive off-label applications across multiple medical specialties. This study synthesizes evidence of the use of Methotrexate in dermatology, gastroenterology, obstetrics and gynecology, rheumatology, ophthalmology, hematology, and emerging applications in infectious diseases and cardiovascular medicine. The evidence base reveals that while MTX demonstrates efficacy in numerous off-label indications. Dermatological applications are supported by low-quality evidence across 31 conditions, while obstetric uses for ectopic pregnancy show 91% efficacy in appropriate clinical scenarios. Gastroenterological applications in Crohn's disease are well-established, though evidence for ulcerative colitis remains limited. Emerging applications in COVID-19 treatment and cardiovascular risk reduction represent promising areas requiring further investigation. Safety profiles are generally acceptable at low doses, though monitoring for hepatotoxicity, hematologic abnormalities, and pulmonary complications remains essential.