The Role and Mechanistic Effects of Methotrexate in the Treatment of Rheumatoid Arthritis

Methotrexate (MTX) remains a cornerstone in the management of rheumatoid arthritis (RA). Extensive basic pharmacological research has consistently demonstrated the e cacy of MTX in treating RA, while there is still insu cient understanding about the potential mechanisms. In this review, current knowledge on the mechanisms by which MTX acts in bone erosion and synovitis is summarized, and MTX-based combination therapies are discussed. Additionally, the bone-protective and anti-in%am matory roles of adenosine receptors are described, and biomarkers associated with MTX responders in RA are explored. This review sheds new light on future research directions for RA, as well as o ers evidence-based recommendations to enhance the clinical utilization of MTX in RA treatment.

Cite this article as: Teng Y, Jiang L, Yin H, Deng G. The role and mechanistic e ects of methotrexate in the treatment of rheumatoid arthritis. Eur J Rheumatol. 2025:12(4), -0086, 10.5152/ eurjrheum.2025.24086.