EDSS variability before randomization may limit treatment discovery in primary progressive MS

Mult Scler. 2013 May;19(6):775-81. doi: 10.1177/1352458512459685. Epub 2012 Oct 1.


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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00087529.

Keywords: EDSS; Multiple sclerosis; PPMS; disability progression; rituximab.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Computer Simulation
  • Disability Evaluation*
  • Disease Progression
  • Double-Blind Method
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Linear Models
  • Male
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / diagnosis*
  • Multiple Sclerosis, Chronic Progressive / drug therapy*
  • Multiple Sclerosis, Chronic Progressive / physiopathology
  • North America
  • Predictive Value of Tests
  • Research Design*
  • Rituximab
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Antibodies, Monoclonal, Murine-Derived
  • Immunosuppressive Agents
  • Rituximab

Associated data

  • ClinicalTrials.gov/NCT00087529