How similar are commonly combined criteria for EDSS progression in multiple sclerosis?
BACKGROUND
Measuring disease progression is an important aspect of multiple sclerosis (MS) clinical trials. Commonly applied disability endpoints include time to clinically meaningful Expanded Disability Status Scale (EDSS) change, or the number of patients in whom such a change has occurred. Typically, clinically meaningful EDSS change has been defined as a change of 1.0 point on Kurtzke's EDSS in patients with an entry EDSS score of 5.5 or lower, or 0.5 point in patients with a higher EDSS score. Our goal was to evaluate whether these changes can be considered as similar. Therefore, we compared EDSS changes to corresponding changes in the Guy's Neurological Disability Scale (GNDS), which is a measure of patient perceived disability, and the Multiple Sclerosis Functional Composite (MSFC), which is an examination-based quantitative scoring of neurological impairment.


METHODS
From a large longitudinal database, we selected two groups of patients with a clinically meaningful change in EDSS score according to the usual criteria: patients with EDSS change > or = 1.0 for baseline EDSS < or = 5.5 and patients with EDSS change > or = 0.5 for baseline EDSS > or = 6.0. We compared changes in GNDS sum score and in MSFC score between both groups.


RESULTS
In the group with baseline EDSS > or = 6.0, GNDS and MSFC changes were higher than in patients with baseline EDSS < or = 5.5. The difference in change was 1.00 (95% confidence interval (CI): -0.35 to 2.36) for the GNDS and 0.412 (95% CI: 0.300-0.525) for the MSFC.


CONCLUSIONS
Our results indicate that a 0.5 point EDSS change in patients with baseline EDSS > or = 6.0 cannot be considered equal to a 1.0 point change in patients with baseline EDSS < or = 5.5.
Kragt
J J
JJ
Department of Neurology, VU University Medical Centre, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands. jj.kragt@vumc.nl
Nielsen
I M
IM
van der Linden
F A H
FA
Uitdehaag
B M J
BM
Polman
C H
CH
D000328:Adult; D002986:Clinical Trials as Topic / Q000379:methods; D016208:Databases, Factual; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000503:physiopathology*; D012720:Severity of Illness Index