title: Magnetic resonance imaging outcomes from a phase III trial of teriflunomide.
abstract: OBJECTIVE
  The purpose of this study was to determine the effects of oral teriflunomide on multiple sclerosis (MS) pathology inferred by magnetic resonance imaging (MRI).
  
  
  METHODS
  Patients (n=1088) with relapsing MS were randomized to once-daily teriflunomide 7 mg or 14 mg, or placebo, for 108 weeks. MRI was recorded at baseline, 24, 48, 72 and 108 weeks. Annualized relapse rate and confirmed progression of disability (sustained ≥12 weeks) were the primary and key secondary outcomes. The principal MRI outcome was change in total lesion volume.
  
  
  RESULTS
  After 108 weeks, increase in total lesion volume was 67.4% (p=0.0003) and 39.4% (p=0.0317) lower in the 14 and 7 mg dose groups versus placebo. Other measures favoring teriflunomide were accumulated enhanced lesions, combined unique activity, T2-hyperintense and T1-hypointense component lesion volumes, white matter volume, and a composite MRI score; all were significant for teriflunomide 14 mg and most significant for 7 mg versus placebo.
  
  
  CONCLUSIONS
  Teriflunomide provided benefits on brain MRI activity across multiple measures, with a dose effect evident on several markers. These effects were also consistent across selected subgroups of the study population. These findings complement clinical data showing significant teriflunomide-related reductions in relapse rate and disease progression, and demonstrate containment of MRI-defined disease progression.
authors: Department of Neurology, The University of Texas Health Science Center at Houston, USA. jerry.s.wolinsky@uth.tmc.edu
authors: Jerry S
authors: JS
authors: Wolinsky
authors: Ponnada A
authors: PA
authors: Narayana
authors: Flavia
authors: F
authors: Nelson
authors: Sushmita
authors: S
authors: Datta
authors: Paul
authors: P
authors: O'Connor
authors: Christian
authors: C
authors: Confavreux
authors: Giancarlo
authors: G
authors: Comi
authors: Ludwig
authors: L
authors: Kappos
authors: Tomas P
authors: TP
authors: Olsson
authors: Philippe
authors: P
authors: Truffinet
authors: Lin
authors: L
authors: Wang
authors: Aaron
authors: A
authors: Miller
authors: Mark S
authors: MS
authors: Freedman
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001921:Brain / Q000473:pathology*; D003437:Crotonates / Q000008:administration & dosage*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D009570:Nitriles; D014052:Toluidines / Q000008:administration & dosage*
chemical_list: D000893:Anti-Inflammatory Agents; D003437:Crotonates; D004791:Enzyme Inhibitors; D006885:Hydroxybutyrates; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide
keywords: Teriflunomide; clinical trial; disease-modifying therapy; magnetic resonance imaging; multiple sclerosis; phase III