title: Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: Interim analysis of ENDORSE, a randomized extension study.
abstract: BACKGROUND
  Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favorable benefit-risk profile for patients with relapsing-remitting multiple sclerosis (RRMS) in phase 3 DEFINE/CONFIRM studies. ENDORSE is an ongoing long-term extension of DEFINE/CONFIRM.
  
  
  OBJECTIVE
  We report efficacy and safety results of a 5-year interim analysis of ENDORSE (2 years DEFINE/CONFIRM; minimum 3 years ENDORSE).
  
  
  METHODS
  In ENDORSE, patients randomized to DMF 240 mg twice (BID) or thrice daily (TID) in DEFINE/CONFIRM continued this dosage, and those initially randomized to placebo (PBO) or glatiramer acetate (GA) were re-randomized to DMF 240 mg BID or TID.
  
  
  RESULTS
  For patients continuing DMF BID (BID/BID), annualized relapse rates were 0.202, 0.163, 0.139, 0.143, and 0.138 (years 1-5, respectively) and 63%, 73%, and 88% were free of new or enlarging T2 hyperintense lesions, new T1 hypointense lesions, and gadolinium-enhanced lesions, respectively, at year 5. Adverse events (AEs; serious adverse events (SAEs)) were reported in 91% (22%; BID/BID), 95% (24%; PBO/BID), and 88% (16%; GA/BID) of the patients. One case of progressive multifocal leukoencephalopathy was reported in the setting of severe, prolonged lymphopenia.
  
  
  CONCLUSIONS
  Treatment with DMF was associated with continuously low clinical and magnetic resonance imaging (MRI) disease activity in patients with RRMS. These interim data demonstrate a sustained treatment benefit and an acceptable safety profile with DMF.
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.affiliation: NeuroRx Research, Montreal, QC, Canada/Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Arnold
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.affiliation: St. Vincent's University Hospital, Dublin, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Hutchinson
authors.affiliation: Department of Neurology, University Hospital of Basel, Basel, Switzerland.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: Department of Neurology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.
authors.forename: David G
authors.initials: DG
authors.lastname: MacManus
authors.affiliation: NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Yousry
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Pozzilli
authors.affiliation: Medical University of Lodz, Lodz, Poland.
authors.forename: Krysztof
authors.initials: K
authors.lastname: Selmaj
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Marianne T
authors.initials: MT
authors.lastname: Sweetser
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Ray
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Minhua
authors.initials: M
authors.lastname: Yang
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Potts
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Novas
authors.affiliation: NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.
authors.forename: David H
authors.initials: DH
authors.lastname: Miller
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Nuwan C
authors.initials: NC
authors.lastname: Kurukulasuriya
authors.affiliation: Cleveland Clinic, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland, OH, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fox
authors.affiliation: Baylor Institute for Immunology Research, Multiple Sclerosis Program, Dallas, TX, USA.
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Phillips
mesh_terms: D000328:Adult; D000069462:Dimethyl Fumarate / Q000627:therapeutic use*; D005260:Female; D000068717:Glatiramer Acetate / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000068717:Glatiramer Acetate; D000069462:Dimethyl Fumarate
keywords: DEFINE; ENDORSE; Expanded Disability Status Scale; Relapsing–remitting multiple sclerosis; delayed-release dimethyl fumarate (DMF)