title: Pegylated interferon β-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study.
abstract: BACKGROUND
  Subcutaneous pegylated interferon (peginterferon) beta-1a is being developed for treatment of relapsing multiple sclerosis, with less frequent dosing than currently available first-line injectable treatments. We assessed the safety and efficacy of peginterferon beta-1a after 48 weeks of treatment in the placebo-controlled phase of the ADVANCE trial, a study of patients with relapsing-remitting multiple sclerosis.
  
  
  METHODS
  We did this 2-year, double-blind, parallel group, phase 3 study, with a placebo-controlled design for the first 48 weeks, at 183 sites in 26 countries. Patients with relapsing-remitting multiple sclerosis (age 18-65 years, with Expanded Disability Status Scale score ≤5) were randomly assigned (1:1:1) via an interactive voice response or web system, and stratified by site, to placebo or subcutaneous peginterferon beta-1a 125 μg once every 2 weeks or every 4 weeks. The primary endpoint was annualised relapse rate at 48 weeks. This trial is registered with ClinicalTrials.gov, number NCT00906399.
  
  
  RESULTS
  We screened 1936 patients and enrolled 1516, of whom 1512 were randomly assigned (500 to placebo, 512 to peginterferon every 2 weeks, 500 to peginterferon every 4 weeks); 1332 (88%) patients completed 48 weeks of treatment. Adjusted annualised relapse rates were 0·397 (95% CI 0·328-0·481) in the placebo group versus 0·256 (0·206-0·318) in the every 2 weeks group and 0·288 (0·234-0·355) in the every 4 weeks group (rate ratio for every 2 weeks group 0·644, 95% CI 0·500-0·831, p=0·0007; rate ratio for the every 4 weeks group 0·725, 95% CI 0·565-0·930, p=0·0114). 417 (83%) patients taking placebo, 481 (94%) patients taking peginterferon every 2 weeks, and 472 (94%) patients taking peginterferon every 4 weeks reported adverse events including relapses. The most common adverse events associated with peginterferon beta-1a were injection site reactions, influenza-like symptoms, pyrexia, and headache. 76 (15%) patients taking placebo, 55 (11%) patients taking study drug every 2 weeks, and 71 (14%) patients taking study drug every 4 weeks reported serious adverse events; relapse, pneumonia, and urinary tract infection were the most common.
  
  
  CONCLUSIONS
  After 48 weeks, peginterferon beta-1a significantly reduced relapse rate compared with placebo. The drug might be an effective treatment for relapsing-remitting multiple sclerosis with less frequent administration than available treatments.
  
  
  BACKGROUND
  Biogen Idec.
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. Electronic address: pcalabr1@jhmi.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, QC, Canada; NeuroRx Research, Montreal, QC, Canada.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Arnold
authors.affiliation: Department of Neurology, New York University, Langone Medical Center, New York, NY, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Balcer
authors.affiliation: Moscow MS Center at 11 City Hospital and Department of Neurology & Neurosurgery of the RSMRU named by Pirogov, Moscow, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Boyko
authors.affiliation: Departments of Neurology and Research (CRMBM), CHU Timone, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: Biogen Idec, Cambridge, MA, USA.
authors.forename: Shifang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Biogen Idec, Cambridge, MA, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Biogen Idec, Cambridge, MA, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Seddighzadeh
authors.affiliation: Biogen Idec, Cambridge, MA, USA.
authors.forename: Serena
authors.initials: S
authors.lastname: Hung
authors.affiliation: Biogen Idec, Cambridge, MA, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Deykin
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D011092:Polyethylene Glycols; D016899:Interferon-beta; D000068556:Interferon beta-1a