Methotrexate + Leucovorin + BMS-986142

This is a combination of three agents: methotrexate, leucovorin, and BMS-986142. Methotrexate is a well-established antimetabolite and antifolate agent used primarily in the treatment of cancer and autoimmune diseases such as rheumatoid arthritis. Leucovorin (also known as folinic acid) is used to reduce the toxic effects of methotrexate by rescuing normal cells from its antifolate activity. BMS-986142 is an investigational, oral small-molecule inhibitor of Bruton’s tyrosine kinase (BTK), developed by Bristol Myers Squibb for autoimmune conditions including rheumatoid arthritis and Sjögren's syndrome. The mechanism of action for this combination involves immunosuppression via inhibition of dihydrofolate reductase (methotrexate), rescue from folic acid antagonism (leucovorin), and selective inhibition of BTK-mediated signaling in B cells (BMS-986142). This combination has been studied in clinical trials to assess safety, pharmacokinetics, and potential synergistic efficacy in autoimmune disease models[1][4][5].