methotrexate + mizoribine + tacrolimus

This is an oral triple combination therapy consisting of methotrexate, mizoribine, and tacrolimus. All three are immunosuppressive agents with distinct mechanisms of action. Methotrexate is a folic acid antagonist that inhibits dihydrofolate reductase, suppressing DNA synthesis and immune cell proliferation. Mizoribine inhibits inosine monophosphate dehydrogenase, blocking purine synthesis in lymphocytes and thus reducing immune activity. Tacrolimus is a calcineurin inhibitor that prevents T-cell activation by inhibiting interleukin-2 transcription. The combination has been studied for use in patients with refractory rheumatoid arthritis (RA), particularly those who do not respond adequately to dual therapy regimens (e.g., methotrexate plus either mizoribine or tacrolimus). In both in vitro studies (showing reduced osteoclast differentiation and activity) and prospective clinical studies, this triple regimen demonstrated significant improvements in disease activity scores compared to single or double agent therapies. The combination also led to decreased serum matrix metalloproteinase-3 levels—a marker of joint inflammation—and was well tolerated without significant adverse effects reported during the study period[6].

Other names

methotrexate + mizoribine + tacrolimus