PT  - JOURNAL ARTICLE
AU  - Young, P. J.
AU  - Lederer, C.
AU  - Eder, K.
AU  - Daumer, M.
AU  - Neiss, A.
AU  - Polman, C.
AU  - Kappos, L.
ED  - ,
TI  - Relapses and subsequent worsening of disability in relapsing-remitting multiple sclerosis
AID  - 10.1212/01.wnl.0000234064.17156.03
DP  - 2006 Sep 12
TA  - Neurology
PG  - 804--808
VI  - 67
IP  - 5
4099  - http://n.neurology.org/content/67/5/804.short
4100  - http://n.neurology.org/content/67/5/804.full
SO  - Neurology2006 Sep 12; 67
AB  - 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). Conclusion: 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.