Cristina Guarnera, Placido Bramanti, Emanuela Mazzon

In the therapeutic scenario of disease-modifying therapies for relapsing-remitting multiple sclerosis, the introduction of oral agents, starting in 2010 with fingolimod, has been a huge step forward in therapeutic options due to the easier administration route. Three oral drugs fingolimod, teriflunomide, and dimethyl fumarate, which are clinically approved for the treatment of relapsing-remitting multiple sclerosis, are reviewed in this work. Results of Phase III clinical trials and their extension studies showed that the three oral agents significantly reduced the annualized relapse rate - a superior efficacy compared to placebo. Fingolimod 0.5 mg consistently reduced clinical relapses and brain volume loss. In all Phase III studies, teriflunomide 14 mg dose showed a reduction in the risk of disability accumulation. Regarding safety profile, fingolimod had more safety issues than the other two agents. For this reason, it should be strictly monitored for risks of infections, cancers, and certain transitory effects such as irregular cardiac function, decreased lymphocyte count, and a higher level of liver enzymes. Adverse effects of teriflunomide are well characterized and can be considered manageable. The main risks marked with dimethyl fumarate were flushing and gastrointestinal events.