title: Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial.
abstract: OBJECTIVE
  To examine the effects of interferon beta (IFNβ)-1b on all-cause mortality over 21 years in the cohort of 372 patients who participated in the pivotal randomized clinical trial (RCT), retaining (in the analysis) the original randomized treatment-assignments.
  
  
  METHODS
  For this randomized long-term cohort study, the primary outcome, defined before data collection, was the comparison of all-cause mortality between the IFNβ-1b 250 μg and placebo groups from the time of randomization through the entire 21-year follow-up interval (intention-to-treat, log-rank test for Kaplan-Meier survival curves). All other survival outcomes were secondary.
  
  
  RESULTS
  After a median of 21.1 years from RCT enrollment, 98.4%(366 of 372) of patients were identified, and, of these, 81 deaths were recorded (22.1% [81 of 366]). Patients originally randomly assigned to IFNβ-1b 250 μg showed a significant reduction in all-cause mortality over the 21-year period compared with placebo (p = 0.0173), with a hazard ratio of 0.532 (95% confidence interval 0.314-0.902). The hazard rate of death at long-term follow-up by Kaplan-Meier estimates was reduced by 46.8% among IFNβ-1b 250 μg-treated patients (46.0% among IFNβ-1b 50 μg-treated patients) compared with placebo. Baseline variables did not influence the observed treatment effect.
  
  
  CONCLUSIONS
  There was a significant survival advantage in this cohort of patients receiving early IFNβ-1b treatment at either dose compared with placebo. Near-complete ascertainment, together with confirmatory findings from both active treatment groups, strengthens the evidence for an IFNβ-1b benefit on all-cause mortality.
  
  
  METHODS
  This study provides Class III evidence that early treatment with IFNβ-1b is associated with prolonged survival in initially treatment-naive patients with relapsing-remitting multiple sclerosis.
authors.affiliation: Department of Neurology, University of California, San Francisco, CA, USA. douglas.goodin@ucsf.edu
authors.forename: D S
authors.initials: DS
authors.lastname: Goodin
authors.forename: A T
authors.initials: AT
authors.lastname: Reder
authors.forename: G C
authors.initials: GC
authors.lastname: Ebers
authors.forename: G
authors.initials: G
authors.lastname: Cutter
authors.forename: M
authors.initials: M
authors.lastname: Kremenchutzky
authors.forename: J
authors.initials: J
authors.lastname: Oger
authors.forename: D
authors.initials: D
authors.lastname: Langdon
authors.forename: M
authors.initials: M
authors.lastname: Rametta
authors.forename: K
authors.initials: K
authors.lastname: Beckmann
authors.forename: T M
authors.initials: TM
authors.lastname: DeSimone
authors.forename: V
authors.initials: V
authors.lastname: Knappertz
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D017668:Age of Onset; D002423:Cause of Death; D005260:Female; D006801:Humans; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000401:mortality*; D016019:Survival Analysis
chemical_list: D000276:Adjuvants, Immunologic; D000068576:Interferon beta-1b; D016899:Interferon-beta