Multiple Sclerosis

Abstract

Several new medicines have been approved or entered development for the treatment of Multiple Sclerosis (MS) in the past few years. The sphingosine‐1‐phosphate (S1P) modulator fingolimod was the first FDA approved oral disease modifying therapy for MS, and it has inspired a number of additional agents directed at this clinically validated target. Fumarates (e.g. dimethyl fumarate), dihydroorotate dehydrogenase inhibitors (e.g. teriflunomide) and other agents which decrease lymphocyte proliferation (e.g. cladribine) represent additional clinically validated therapeutic approaches. While the mechanisms of action for these new agents may not be fully defined, they have demonstrated a good degree of efficacy in the treatment of relapsing forms of MS. It is of interest to note that biologic agents which target CD20 on B cells have also shown significant efficacy in the treatment of MS. This, in turn, has spurred MS clinical trials with Bruton's Tyrosine Kinase (BTK) inhibitors, which also act on B cell pathways. The introduction of each of these newer agents still requires careful consideration of the risk–benefit for individual patients, but has also set a higher bar in the treatment of MS for subsequent agents, as evidenced by the discontinuation of several agents in late stage clinical trials. This higher bar has also pushed some historic agents to second or third line agents. This speaks to an overall advancement in the treatment of MS, and provides hope for further advances in therapeutic options.