dimethyl fumarate + teriflunomide

This is a combination of two oral small molecule disease-modifying therapies used in the treatment of relapsing forms of multiple sclerosis (MS): dimethyl fumarate and teriflunomide. Dimethyl fumarate acts primarily by activating the Nrf2 pathway, leading to anti-inflammatory and cytoprotective effects, and suppresses pro-inflammatory gene expression via inhibition of nuclear factor kappa B. It also shifts immune cell phenotypes from pro-inflammatory to anti-inflammatory states. Teriflunomide is an immunomodulatory agent that selectively and reversibly inhibits dihydro-orotate dehydrogenase (DHODH), a key enzyme in de novo pyrimidine synthesis, thereby reducing proliferation of activated T and B lymphocytes involved in MS pathogenesis[6][8]. Both drugs are approved as monotherapies for relapsing-remitting MS; however, there is no evidence or approval for their use as a fixed-dose combination product.