Safety of teriflunomide for the management of relapsing-remitting multiple sclerosis

Abstract

Introduction: Teriflunomide is a new oral disease-modifying drug (DMD), recently approved for the first-line treatment of relapsing multiple sclerosis (MS). Since MS is a chronic disease, which often necessitates long-term treatment, data not only on efficacy but also on long-term safety, including pregnancy-related issues, are very important.

Areas covered: In this review article, we outline the key preclinical and clinical data on teriflunomide with a focus on its safety profile. We summarize adverse events observed in the Phase II and III clinical trials and the safety data from the long-term extension phases as well as the > 15-year post-marketing experience with the parent drug, leflunomide. We also consider the evidence regarding immune competence and potential fetal risks of the drug.

Expert opinion: Teriflunomide has the advantage of a convenient once-daily oral administration scheme and a large body of evidence suggesting a manageable safety profile (clinical development program with > 6800 patient-years of exposure and post-marketing experience with leflunomide). Further post-marketing data, especially regarding pregnancy outcomes and risks of infections, will help to define the exact place of teriflunomide in the treatment of MS in the future, especially compared with the other oral DMDs.

Keywords:

• DHODH-inhibition
• hair thinning
• leflunomide
• multiple sclerosis
• safety profile
• teratogenicity
• teriflunomide

Declaration of interest

A Papadopoulou has consulted for Teva, received travel support from Bayer AG, UCB-Pharma and Teva and lecture honoraria from Genzyme and Novartis, which were used exclusively for research in the University Hospital of Basel. T Sprenger has consulted for Genzyme, Novartis, Mitsubishi Pharma and Biogen Idec. He received travel support from Genzyme and Bayer Schering and has received research support from Novartis Pharmaceuticals Switzerland. L Kappos’ institution (University Hospital Basel) received in the last 3 years and used exclusively for research support: steering committee, advisory board and consultancy fees from Actelion, Addex, Bayer Health Care, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, UCB, Xenoport; speaker fees from Bayer Health Care, Biogen, Merck, Novartis, Sanofi-Aventis, Teva; support of educational activities from Bayer Health Care, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; royalties from Neurostatus Systems GmbH; and grants from Bayer Health Care, Biogen, Merck, Novartis, Roche and Roche Research Foundations. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.