title: Teriflunomide: a review of its use in relapsing multiple sclerosis.
abstract: Teriflunomide (Aubagio™) is the main active metabolite of leflunomide, an established disease-modifying anti-rheumatic drug. Teriflunomide is an inhibitor of de novo pyrimidine synthesis, reducing lymphocyte proliferation, amongst other immunomodulatory effects; autoimmunity is believed to be one of the potential mechanisms of disease for multiple sclerosis. Teriflunomide is considered cytostatic but not cytotoxic: it does not affect resting or slowly dividing lymphocytes. This article reviews the available pharmacological properties of oral teriflunomide and its clinical efficacy and tolerability in patients with relapsing multiple sclerosis. While both the 7 and the 14 mg/day dosages are discussed, the 7 mg/day dosage is not approved in the EU. Both dosages are approved in the USA. In phase III trials, teriflunomide 7 or 14 mg/day was consistently demonstrated to be more effective than placebo and as effective as interferon beta-1a in the prevention of relapses in patients with relapsing forms of multiple sclerosis; moreover, teriflunomide 14 mg/day was also consistently shown to be more effective than placebo in prevention of disability progression. Teriflunomide was generally well tolerated in these patients. Long-term, extension data were generally similar to those observed in the shorter-term trials. Teriflunomide is associated with increased liver enzyme levels, and is contraindicated in pregnant patients because of a potential risk of teratogenicity. As an oral treatment, it offers an alternative to the traditional, parenteral, disease-modifying therapies; however, further investigation into the efficacy and/or tolerability differences between teriflunomide and other available oral drugs would be of great use in the placement of this drug. At present, given the relatively limited long-term data, it is difficult to draw definite conclusions with regard to safety; however, as teriflunomide is the main active metabolite of leflunomide, long-term safety data can be extrapolated from the large amount of post-approval data available regarding its parent drug. Oral teriflunomide is a valuable addition to available treatment options for patients with relapsing multiple sclerosis, in particular those patients who prefer an oral drug.
authors.affiliation: Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand, demail@springer.com.
authors.forename: Karly P
authors.initials: KP
authors.lastname: Garnock-Jones
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000737:chemistry / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods; D003437:Crotonates / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates; D007155:Immunologic Factors / Q000737:chemistry / Q000627:therapeutic use*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D009570:Nitriles; D011247:Pregnancy; D014052:Toluidines / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D018501:Antirheumatic Agents; D003437:Crotonates; D006885:Hydroxybutyrates; D007155:Immunologic Factors; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide