title: Disability progression in a clinical trial of relapsing-remitting multiple sclerosis: eight-year follow-up.
abstract: OBJECTIVE
  To investigate the value of Expanded Disability Status Scale (EDSS) worsening sustained for at least 6 months and other parameters as predictors for disability status.
  
  
  METHODS
  Retrospective analysis of the Multiple Sclerosis Collaborative Research Group study data.
  
  
  METHODS
  The intramuscular interferon beta-1a pivotal trial was a double-blind, placebo-controlled phase 3 study.
  
  
  METHODS
  Patients with relapsing-remitting multiple sclerosis who received at least 2 years of treatment and completed an EDSS evaluation 8 years postrandomization.
  
  
  METHODS
  Thirty micrograms of intramuscular interferon beta-1a or placebo once weekly during the 2-year clinical trial.
  
  
  METHODS
  Positive predictive values for 6-month sustained progression during 2 years were calculated to determine the ability to predict disability status at 8 years. A multivariate logistic regression model was used to assess the relationship between predictors and EDSS milestones at follow-up.
  
  
  RESULTS
  Forty-five patients had sustained 6-month EDSS progression during the clinical trial and 115 did not. Progression during the trial was the strongest predictor of reaching EDSS milestones at the follow-up visit, 8 years after randomization. Other independent predictors were treatment arm assignment and baseline EDSS score.
  
  
  CONCLUSIONS
  In this phase 3 clinical trial of intramuscular interferon beta-1a, compared with effects of treatment, baseline EDSS score, and number of relapses during the study, worsening of 1 point or more on EDSS from baseline lasting 6 months was the strongest predictor of clinically significant disability 8 years after randomization into the clinical trial.
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA. rudickr@ccf.org
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rudick
authors.forename: Jar-Chi
authors.initials: JC
authors.lastname: Lee
authors.forename: Gary R
authors.initials: GR
authors.lastname: Cutter
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Miller
authors.forename: Dennis
authors.initials: D
authors.lastname: Bourdette
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: Robert
authors.initials: R
authors.lastname: Hyde
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: You
mesh_terms: D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007273:Injections, Intramuscular; D016899:Interferon-beta / Q000627:therapeutic use*; D016015:Logistic Models; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D016899:Interferon-beta