title: High-dose erythropoietin in patients with progressive multiple sclerosis: A randomized, placebo-controlled, phase 2 trial.
abstract: BACKGROUND
  Erythropoietin (EPO) is a part of an endogenous neuroprotective system in the brain and may address pathophysiological mechanisms in progressive multiple sclerosis (MS).
  
  
  OBJECTIVE
  To evaluate a treatment effect of EPO on progressive MS.
  
  
  METHODS
  This was a single-center, randomized, double-blind, placebo-controlled phase 2 trial, in which 52 patients with secondary or primary progressive MS were allocated to treatment with recombinant EPO (48,000 IU) or placebo, administered intravenously 17 times during 24 weeks. Patients had an Expanded Disability Status Score (EDSS) from 4 to 6.5 and clinical progression without relapses in the 2 preceding years. The primary outcome was the change in a composite measure of maximum gait distance, hand dexterity, and cognition from baseline to 24 weeks.
  
  
  RESULTS
  A total of 50 patients completed the study. Venesection was performed often but no thromboembolic events occurred. We found no difference in the primary outcome between the EPO and the placebo group using the intention-to-treat principle ( p = 0.22). None of the secondary outcomes, neither clinical nor magnetic resonance imaging (MRI) measures showed any significant differences.
  
  
  CONCLUSIONS
  This study provides class II evidence that treatment with high-dose EPO is not an effective treatment in patients with moderately advanced progressive MS.
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Schreiber
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Melinda
authors.initials: M
authors.lastname: Magyari
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Finn
authors.initials: F
authors.lastname: Sellebjerg
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Iversen
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ellen
authors.initials: E
authors.lastname: Garde
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Camilla Gøbel
authors.initials: CG
authors.lastname: Madsen
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Börnsen
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Romme Christensen
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Ratzer
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark/Department of Neurology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hartwig Roman
authors.initials: HR
authors.lastname: Siebner
authors.affiliation: University of Southern Denmark, Odense, Denmark.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Laursen
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Soelberg Sorensen
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D004921:Erythropoietin
keywords: Erythropoietin; progressive multiple sclerosis