title: From Leflunomide to Teriflunomide: Drug Development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis.
abstract: BACKGROUND
  Immunosuppressive drugs have been used in the treatment of multiple sclerosis (MS) for a long time. Today, orally available second generation immunosuppressive agents have been approved or are filed for licensing as MS therapeutics. Due to semi-selective targeting of cellular processes, these second-generation immunosuppressive compounds might rather be immunomodulatory. For example, Teriflunomide inhibits the de novo pyrimidine synthesis and thus only targets rapidly proliferating cells, including lymphocytes. It is used as first line disease modifying therapy (DMT) in relapsing-remitting MS (RRMS).
  
  
  METHODS
  Review of online content related to oral immunosuppressants in MS with an emphasis on Teriflunomide.
  
  
  RESULTS
  Teriflunomide and Cladribine are second-generation immunosuppressants that are efficient in the treatment of MS patients. For Teriflunomide, a daily dose of 14 mg reduces the annualized relapse rate (ARR) by more than 30% and disability progression by 30% compared to placebo. Cladribine reduces the ARR by about 50% compared to placebo but has not yet been licensed due to unresolved safety concerns. We also discuss the significance of older immunosuppressive compounds including Azathioprine, Mycophenolate mofetile, and Cyclophosphamide in current MS therapy.
  
  
  CONCLUSIONS
  Teriflunomide has shown a favorable safety and efficacy profile in RRMS and is a therapeutic option for a distinct group of adult patients with RRMS.
authors.affiliation: Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstraße 22, 81675 Munich. Germany.
authors.forename: Lilian
authors.initials: L
authors.lastname: Aly
authors.affiliation: Department of Neurology, Technische Universität München, Ismaningerstraße 22, 81675 Munich. Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
authors.affiliation: Department of Neurology, Technische Universität München, Ismaningerstraße 22, 81675 Munich. Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Korn
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003437:Crotonates / Q000008:administration & dosage*; D055808:Drug Discovery; D006801:Humans; D006885:Hydroxybutyrates; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007555:Isoxazoles / Q000008:administration & dosage*; D000077339:Leflunomide; D009103:Multiple Sclerosis / Q000188:drug therapy*; D009570:Nitriles; D014052:Toluidines / Q000008:administration & dosage*
chemical_list: D003437:Crotonates; D006885:Hydroxybutyrates; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D000077339:Leflunomide
keywords: Disease modifying therapy; immunosuppression; leflunomide; multiple sclerosis; oral; teriflunomide