Predicting the On-Study Relapse Rate for Multiple Sclerosis Patients in Clinical Trials

Background: The annual relapse rate has been commonly used as a
primary efficacy endpoint in phase III multiple sclerosis (MS)
clinical trials. The aim of this study was to determine the
relative contribution of different possible prognostic factors
available at baseline to the on-study relapse rate in MS. Methods:
A total of 821 patients from the placebo arms of the Sylvia Lawry
Centre for Multiple Sclerosis Research (SLCMSR) database were
available for this analysis. The univariate relationships between
on-study relapse rate and the baseline demographic, clinical, and
MRI-based predictors were assessed. The multiple relationships were
then examined using a Poisson regression model. Two predictor
subsets were selected. Subset 1 included age at disease onset,
disease duration, gender, Expanded Disability Status Scale (EDSS)
at baseline, number of relapses in the last 24 months prior to
baseline, and the disease course (RR and SP). Subset 2 consisted of
Subset 1 plus gadolinium enhancement status in MRI. The number of
patients for developing the models with no missing values was 727
for Subset 1 and 306 for Subset 2. Results:The univariate
relationships show that the on-study relapse rate was higher for
younger and for female patients, for RR patients than for SP
patients, and for patients with positive enhancement status at
entry (Wilcoxon test, p