Teriflunomide for treatment of multiple sclerosis

Interferon beta and glatiramer acetate are still considered to be the first-line therapeutics for treatment of relapsing forms of multiple sclerosis (MS). The use of new compounds, such as natalizumab or fingolimod, is restricted to severe forms of relapsing MS or cases refractory to first-line treatment owing to substance-specific risk-benefit considerations. Teriflunomide is a new compound which has recently been approved as a first-line treatment of relapsing forms of MS in the USA and Australia. It is characterized by a once daily oral administration and a comparably well-established long-term safety profile. The main therapeutic effect is considered to be mediated via the inhibition of the de novo synthesis of pyrimidine in proliferating immune cells. The pro-drug of teriflunomide, leflunomide, has a label for treating rheumatoid arthritis (RA) for many years. Two recently published phase III clinical trials (TEMSO, TOWER) tested teriflunomide in patients with relapsing forms of MS and efficacy was demonstrated, with positive effects on relapse rates and disease progression using 14 mg/day. Overall, the safety profile in these studies was favorable as expected from experiences with leflunomide in RA. In patients treated with teriflunomide regular monitoring of blood cell counts and liver enzymes is required. Teriflunomide must not be used during pregnancy. In this article the recent phase II and phase III clinical trial data are reviewed and the potential of teriflunomide for the treatment of relapsing forms of MS is discussed.