title: Relationship between sustained disability progression and functional system scores in relapsing-remitting multiple sclerosis: analysis of placebo data from four randomized clinical trials.
abstract: BACKGROUND
  The Expanded Disability Status Scale (EDSS), based on different functional system scores (FSS), remains the most frequently used disability assessment in relapsing-remitting multiple sclerosis (RRMS). In this analysis, we evaluated the relationship between sustained disability progression, measured by EDSS, and simultaneous changes in individual FSS domains.
  
  
  METHODS
  A post hoc analysis was performed on data from placebo-treated RRMS patients from four large, randomized, multicenter, phase 3 clinical trials. Sustained disability progression was defined as a ≥1.0-point EDSS score increase over a ≥3- or ≥6-month period. Simultaneous sustained disability progression and worsening of individual FSS domains was analyzed.
  
  
  RESULTS
  The majority of patients experienced sustained disability progression and simultaneous worsening of ≥1 FSS domain, with ≥1-point worsening in the pyramidal domain being most frequently associated with sustained disability progression (in 31-51% of patients), followed by ≥1-point worsening in the cerebellar (35-41% of patients) and sensory (31-45% of patients) domains.
  
  
  CONCLUSIONS
  The key FSS components correlating with sustained disability progression, measured by EDSS, appear to be pyramidal, cerebellar, and sensory. In this analysis, the simultaneous worsening of consistent FSS domains confirms the validity and reliability of the use of sustained EDSS progression as a measure of disability progression.
authors: Allegheny General Hospital, Pittsburgh, Pa., USA.
authors: Thomas
authors: T
authors: Scott
authors: Ping
authors: P
authors: Wang
authors: Xiaojun
authors: X
authors: You
authors: Monica
authors: M
authors: Mann
authors: Bjørn
authors: B
authors: Sperling
mesh_terms: D000293:Adolescent; D000328:Adult; D000069462:Dimethyl Fumarate / Q000627:therapeutic use; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D000069442:Natalizumab / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D000069442:Natalizumab; D000069462:Dimethyl Fumarate; D000068556:Interferon beta-1a