Relapses and subsequent worsening of disability in relapsing-remitting multiple sclerosis.
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.
Young
P J
PJ
Sylvia Lawry Centre for Multiple Sclerosis Research, Munich, Germany.
Lederer
C
C
Eder
K
K
Daumer
M
M
Neiss
A
A
Polman
C
C
Kappos
L
L
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