title: Time course of clinical and neuroradiological effects of delayed-release dimethyl fumarate in multiple sclerosis.
abstract: OBJECTIVE
  Delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF), demonstrated efficacy and safety in relapsing-remitting multiple sclerosis in the 2-year, randomized, placebo-controlled, phase 3 DEFINE and CONFIRM trials. A post hoc analysis of integrated data from DEFINE and CONFIRM was conducted to determine the temporal profile of the clinical and neuroradiological effects of DMF.
  
  
  METHODS
  Eligible patients were randomized to receive placebo, DMF 240 mg twice (BID) or three times (TID) daily or glatiramer acetate (GA; reference comparator; CONFIRM only) for up to 96 weeks. Patients in the GA group were excluded from this analysis.
  
  
  RESULTS
  A total of 2301 patients were randomized and received treatment with placebo (n = 771) or DMF BID (n = 769) or TID (n = 761). DMF significantly reduced the annualized relapse rate beginning in weeks 0-12 (BID, P = 0.0159; TID, P = 0.0314); the proportion of patients relapsed beginning at week 10 (BID, P = 0.0427) and week 12 (TID, P = 0.0451); and the proportion of patients with 12-week confirmed disability progression beginning at week 62 (BID, P = 0.0454) and week 72 (TID, P = 0.0399), compared with placebo. These effects were sustained throughout the 2-year study period. DMF significantly reduced the odds of having a higher number of gadolinium-enhancing lesions by 88% (BID) and 75% (TID) and the mean number of new or enlarging T2 lesions by 72% (BID) and 67% (TID), from the first post-baseline magnetic resonance imaging assessment at 24 weeks (all P < 0.0001 versus placebo).
  
  
  CONCLUSIONS
  In phase 3 clinical trials, DMF demonstrated rapid and sustained clinical and neuroradiological efficacy in relapsing-remitting multiple sclerosis.
authors.affiliation: Neurology, University Hospital, Basel, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Kappos
authors.forename: G
authors.initials: G
authors.lastname: Giovannoni
authors.forename: R
authors.initials: R
authors.lastname: Gold
authors.forename: J T
authors.initials: JT
authors.lastname: Phillips
authors.forename: D L
authors.initials: DL
authors.lastname: Arnold
authors.forename: C
authors.initials: C
authors.lastname: Hotermans
authors.forename: A
authors.initials: A
authors.lastname: Zhang
authors.forename: V
authors.initials: V
authors.lastname: Viglietta
authors.forename: R J
authors.initials: RJ
authors.lastname: Fox
mesh_terms: D000328:Adult; D003692:Delayed-Action Preparations; D000069462:Dimethyl Fumarate; D005260:Female; D005650:Fumarates / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D005650:Fumarates; D007166:Immunosuppressive Agents; D000069462:Dimethyl Fumarate
keywords: MRI; delayed-release dimethyl fumarate; disability; multiple sclerosis; relapse; time course