title: EDSS variability before randomization may limit treatment discovery in primary progressive MS.
abstract: BACKGROUND
  Baseline Expanded Disability Status Scale (EDSS) is usually based on a single measurement. Here we evaluated whether using a baseline EDSS derived from two pre-treatment measurements improves the detection of progression events and the ability to demonstrate a therapeutic effect in delaying MS disability progression.
  
  
  METHODS
  Real data from OLYMPUS, a phase II/III randomized, placebo-controlled trial of rituximab in patients with primary progressive multiple sclerosis (PPMS), as well as simulated data were analyzed. Several definitions of baseline EDSS were used to capture sustained disability progression (SDP) events. Variations in the EDSS were estimated by linear mixed-effect models.
  
  
  RESULTS
  Selecting the higher of two baseline EDSS scores lowered the number of SDP events in both treatment groups, so decreasing sensitivity, and reduced the number of false SDP events, so increasing specificity. Conversely, selecting the lower of two baseline scores increased sensitivity but decreased specificity. Increased power (~7% based on the simulation study) was observed when the average of screening and Week 0 EDSS scores was used for baseline.
  
  
  CONCLUSIONS
  Baseline EDSS derived from two pre-treatment EDSS measurements may enhance the ability of detecting a therapeutic effect in slowing disability progression in PPMS. This strategy could be implemented in future clinical trials of patients with MS.
authors.affiliation: Genentech Inc., South San Francisco, CA 94080, USA. zhang.jiameng@gene.com
authors.forename: Jiameng
authors.initials: J
authors.lastname: Zhang
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Waubant
authors.forename: Gary
authors.initials: G
authors.lastname: Cutter
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Wolinsky
authors.forename: Robert
authors.initials: R
authors.lastname: Glanzman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D003198:Computer Simulation; D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D009656:North America; D011237:Predictive Value of Tests; D012107:Research Design; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007166:Immunosuppressive Agents; D000069283:Rituximab