adalimumab + methotrexate + ustekinumab

This is a combination therapy consisting of three agents—adalimumab, methotrexate, and ustekinumab—used primarily in the management of refractory or biologic-experienced Crohn’s disease. Adalimumab is a monoclonal antibody targeting tumor necrosis factor alpha (TNF-α), thereby reducing inflammation. Methotrexate is a small molecule antimetabolite that inhibits dihydrofolate reductase, suppressing immune cell proliferation and modulating inflammatory responses. Ustekinumab is a monoclonal antibody that targets the p40 subunit shared by interleukin-12 (IL-12) and interleukin-23 (IL-23), inhibiting their pro-inflammatory signaling pathways. This triple therapy has been reported in case studies to induce clinical remission in patients with Crohn’s disease who have failed previous biologic therapies. The rationale for combining these agents lies in their complementary mechanisms of action targeting different inflammatory pathways.