Efficacy and Safety of Oral Therapies for Relapsing-Remitting Multiple Sclerosis

Disease-modifying therapies have now become standard treatment for multiple sclerosis. These include five oral therapies for relapsing-remitting multiple sclerosis, namely fingolimod, dimethyl fumarate, teriflunomide, cladribine, and siponimod, although there is some discrepancy on the relative efficacy and safety of these agents. To gain further insight on these oral agents in relapsing-remitting multiple sclerosis, we performed a narrative review of fingolimod, dimethyl fumarate, teriflunomide, cladribine, and siponimod. We limited the analysis to randomized clinical studies in which a comparator was used (i.e., placebo or other disease-modifying therapy). As relapsing-remitting multiple sclerosis is a chronic disease and treatment is lifelong, long-term outcomes were an additional focus. A total of 37 studies met inclusion criteria: 15 for fingolimod, 8 for dimethyl fumarate, 7 for teriflunomide, 4 for cladribine, and 3 for siponimod. All drugs showed some functional and magnetic resonance imaging benefit in nearly all clinical studies. The reduction in annual relapse rate was similar for fingolimod, dimethyl fumarate, and cladribine, and somewhat greater than for teriflunomide; there is limited information on the annual relapse rate for siponimod. For all drugs, the benefits reported at short follow-up times are broadly consistent with those seen at longer follow-up times. For fingolimod and dimethyl fumarate, there was a definite trend towards a progressively lower annual relapse rate with continuing treatment. The safety profile of all five drugs was considered to be acceptable, even after extended treatment. While these results should be treated with caution, they highlight that future head-to-head studies are needed to better understand the long-term benefits of disease-modifying therapies. Such information will be of value when considering the risk-benefit profile of these oral therapies.