title: Teriflunomide added to interferon-β in relapsing multiple sclerosis: a randomized phase II trial.
abstract: OBJECTIVE
  To evaluate teriflunomide as add-on therapy to ongoing stable-dosed interferon-β (IFNβ) in patients with relapsing forms of multiple sclerosis (RMS).
  
  
  METHODS
  A total of 118 patients with RMS were randomly assigned 1:1:1 to receive oral placebo or teriflunomide, 7 or 14 mg, once daily for 24 weeks; 86 patients entered the 24-week extension. The primary objective was to evaluate safety; secondary objectives were to evaluate the effects of treatment on disease activity assessed by MRI and relapse rate.
  
  
  RESULTS
  Teriflunomide was well tolerated with a low and similar incidence of treatment-emergent adverse events (TEAEs) across the 3 groups; TEAEs led to treatment discontinuation of 4.9%, 8.1%, and 7.9% of patients in the placebo, 7-mg, and 14-mg groups, respectively. The number of gadolinium-enhancing T1 (T1-Gd) lesions was reduced in both teriflunomide groups, with relative risk reductions (RRRs) of 84.6% (p = 0.0005) and 82.8% (p < 0.0001) for 7 and 14 mg, respectively, compared with IFNβ alone at 48 weeks. T1-Gd lesion volume was also reduced in the 7-mg group (RRR 72.1%, p = 0.1104) and 14-mg group (RRR 70.6%, p = 0.0154). A trend toward dose-dependent reduction in annualized relapse rate was also noted (RRRs 32.6% [p = 0.4355] and 57.9% [p = 0.1005] for 7 and 14 mg, respectively).
  
  
  CONCLUSIONS
  Teriflunomide as add-on therapy to IFNβ had acceptable safety and tolerability and reduced MRI disease activity compared with IFNβ alone.
  
  
  METHODS
  This study provides Class II evidence that teriflunomide, 7 and 14 mg, added to IFNβ, is safe. The T1-Gd lesion burden was significantly reduced with both teriflunomide doses.
authors.affiliation: University of Ottawa, Ottawa, Canada. mfreedman@toh.on.ca
authors.forename: M S
authors.initials: MS
authors.lastname: Freedman
authors.forename: J S
authors.initials: JS
authors.lastname: Wolinsky
authors.forename: B
authors.initials: B
authors.lastname: Wamil
authors.forename: C
authors.initials: C
authors.lastname: Confavreux
authors.forename: G
authors.initials: G
authors.lastname: Comi
authors.forename: L
authors.initials: L
authors.lastname: Kappos
authors.forename: T P
authors.initials: TP
authors.lastname: Olsson
authors.forename: A
authors.initials: A
authors.lastname: Miller
authors.forename: H
authors.initials: H
authors.lastname: Benzerdjeb
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Simonson
authors.forename: P W
authors.initials: PW
authors.lastname: O'Connor
mesh_terms: D000328:Adult; D003437:Crotonates / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates; D016899:Interferon-beta / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D009570:Nitriles; D012720:Severity of Illness Index; D014052:Toluidines / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D003437:Crotonates; D006885:Hydroxybutyrates; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D016899:Interferon-beta