BMS-986142 + methotrexate

BMS-986142 + methotrexate is a combination of an investigational **small molecule oral inhibitor of Bruton’s tyrosine kinase (BTK)** (BMS-986142) and **methotrexate**, commonly used as a standard-of-care disease-modifying antirheumatic drug. BMS-986142 acts as a reversible inhibitor of BTK, a kinase critical for B-cell receptor signaling, cytokine production, co-stimulatory molecule expression, and osteoclastogenesis, relevant in autoimmune diseases such as rheumatoid arthritis. Methotrexate is a folate antagonist that inhibits dihydrofolate reductase, suppressing immune function and inflammation. The combination has been studied in both healthy participants (for safety and pharmacokinetics) and in patients with moderate-to-severe rheumatoid arthritis who had inadequate response to methotrexate. In clinical and preclinical studies, the combination did not significantly affect the pharmacokinetics of methotrexate and showed a well-tolerated safety profile, but in trials efficacy endpoints were not met compared to placebo in patients with rheumatoid arthritis. Preclinical data suggest additive benefit on disease activity, inflammation, and bone damage when both drugs are combined, compared to either alone[1][2][3][5].