title: Efficacy and safety of delayed-release dimethyl fumarate in patients newly diagnosed with relapsing-remitting multiple sclerosis (RRMS).
abstract: BACKGROUND
  Delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in the Phase 3 DEFINE and CONFIRM trials.
  
  
  OBJECTIVE
  To evaluate delayed-release DMF in newly diagnosed relapsing-remitting multiple sclerosis (RRMS) patients, in a post-hoc analysis of integrated data from DEFINE and CONFIRM.
  
  
  METHODS
  Patients included in the analysis were diagnosed with RRMS within 1 year prior to study entry and naive to MS disease-modifying therapy.
  
  
  RESULTS
  The newly diagnosed population comprised 678 patients treated with placebo (n = 223) or delayed-release DMF 240 mg BID (n = 221) or TID (n = 234). At 2 years, delayed-release DMF BID and TID reduced the annualized relapse rate by 56% and 60% (both p < 0.0001), risk of relapse by 54% and 57% (both p < 0.0001), and risk of 12-week confirmed disability progression by 71% (p < 0.0001) and 47% (p = 0.0085) versus placebo. In a subset of patients (MRI cohort), delayed-release DMF BID and TID reduced the mean number of new or enlarging T2-hyperintense lesions by 80% and 81%, gadolinium-enhancing lesion activity by 92% and 92%, and mean number of new non-enhancing T1-hypointense lesions by 68% and 70% (all p < 0.0001 versus placebo). Flushing and gastrointestinal events were associated with delayed-release DMF.
  
  
  CONCLUSIONS
  Delayed-release DMF improved clinical and neuroradiological outcomes relative to placebo in newly diagnosed RRMS patients.
authors.affiliation: St. Josef Hospital, Ruhr University, Germany ralf.gold@ruhr-uni-bochum.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.affiliation: Queen Mary University of London, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.affiliation: Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX, USA.
authors.forename: J Theodore
authors.initials: JT
authors.lastname: Phillips
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fox
authors.affiliation: Biogen Idec, Inc., Cambridge, MA, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Biogen Idec, Inc., Cambridge, MA, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Meltzer
authors.affiliation: Biogen Idec, Inc., Cambridge, MA, USA.
authors.forename: Nuwan C
authors.initials: NC
authors.lastname: Kurukulasuriya
mesh_terms: D000328:Adult; D017326:Clinical Trials, Phase III as Topic; D003692:Delayed-Action Preparations; D000069462:Dimethyl Fumarate; D005260:Female; D005650:Fumarates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / 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: Delayed-release dimethyl fumarate; efficacy; multiple sclerosis; newly diagnosed; safety