Abstract
Objective This study aims to identify the baseline profile characteristic of super-responders to siponimod in the Phase 3 EXPAND study on four domains of progression (Expanded Disability Status Scale [EDSS]; upper limb function using the 9-hole peg test [9HPT]; ambulation using the timed-25-fooot walk test [T25FWT]; and cognitive processing speed using the single digit modalities test [SDMT]) using and innovative statistical approach
Methods This is a post-hoc analysis of the phase III EXPAND trial comparing siponimod (n=1099) vs placebo (n=546) in SPMS. A response score was derived from baseline characteristics describing participants with a more pronounced treatment effect on each of the 4 clinical endpoints and evaluated optimal division into non-responders/responders according to Zhao L et al. 2013.
Results In the whole cohort, the effect of siponimod on time to confirmed progression for each of the 4 outcomes was:
EDSS: HR=0.79, p=0.0103;
9HPT: HR=0.86, p=0.23;
T25FW: HR=0.95, p=0.53;
SDMT: HR=0.75, p=0.001.
Four different responder profiles (RSP) were obtained and validated, all showing a significant interaction with treatment, thus defining responders to each of the 4 outcomes. Overall, 1290/1645(78%) patients were pronounced siponimod-treatment responders in at least one of the 4 clinical outcomes.
Conclusions 78% of SPMS patients had a large treatment benefit with siponimod on at least one of the 4 clinical outcomes.
