title: Relapses and subsequent worsening of disability in relapsing-remitting multiple sclerosis.
abstract: OBJECTIVE
  To investigate whether relapses contribute to the development of subsequent sustained increase of impairment and disability in patients with multiple sclerosis (MS).
  
  
  METHODS
  In a random sampled subset of 256 relapsing-remitting MS (RRMS) patients from the placebo arms of 20 randomized, controlled clinical trials contained in the Sylvia Lawry Centre for MS Research (SLCMSR) open database (mean follow-up time 2.66 years), the authors tested whether time to an increase of the Expanded Disability Status Scale (EDSS) score (confirmed after 6 months) was related to the occurrence of prior relapses. In the primary analysis, EDSS progressions starting within the period used to calculate the on-study relapse rate (sacrifice period) were not counted. The result obtained was then validated in an independent validation part of the SLCMSR database (n = 320).
  
  
  RESULTS
  Although in the first subset of 256 RRMS patients, occurrence of relapses in the first 4 months on study appeared to be the best predictor for a shorter time to subsequent sustained increase in the EDSS score (hazard ratio [HR] 2.26 [95% CI: 1.36 to 3.75]), this finding was not confirmed in the validation dataset (HR 1.35, one-sided Wald test, lower limit of the 95% CI: 0.90).
  
  
  CONCLUSIONS
  Although relapses may result into permanent damage and Expanded Disability Status Scale (EDSS) progression, there is no consistent effect of on-study relapses on the subsequent development of sustained EDSS score increase during a typical clinical study observation period.
authors.affiliation: Sylvia Lawry Centre for Multiple Sclerosis Research, Munich, Germany.
authors.forename: P J
authors.initials: PJ
authors.lastname: Young
authors.forename: C
authors.initials: C
authors.lastname: Lederer
authors.forename: K
authors.initials: K
authors.lastname: Eder
authors.forename: M
authors.initials: M
authors.lastname: Daumer
authors.forename: A
authors.initials: A
authors.lastname: Neiss
authors.forename: C
authors.initials: C
authors.lastname: Polman
authors.forename: L
authors.initials: L
authors.lastname: Kappos
mesh_terms: D000328:Adult; D019992:Databases as Topic; D004185:Disability Evaluation; D006233:Persons with Disabilities; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000453:epidemiology* / Q000503:physiopathology*; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013997:Time Factors