Abstract Details

Title Estimating the profile of responders to treatment in the phase 3 EXPAND trial: do different patients show benefits on different outcomes?

Topic Multiple Sclerosis

Presentation(s) P16 - Poster Session 16 (8:00 AM-9:00 AM)

Poster/Presentation
Number 12-008

Objective

Adopt an innovative statistical approach combining the concept of defining responders to a therapy according to their baseline profile evaluating multiple endpoints.

Background

Different clinical and demographic patient profiles may respond differently to treatment depending on the underlying pathophysiology driving a particular clinical outcome and a therapy’s MOA.

Design/Methods This post-hoc analysis of EXPAND compared siponimod (n=1099) vs placebo (n=546) in SPMS. We generated a response score derived from baseline characteristics describing participants with a more pronounced treatment effect on each of 4 clinical endpoints (EDSS, T25FW, 9HPT, SDMT) and evaluated optimal division into nonresponders/responders according to Zhao L et al. 2013. For good generalization performance training-validation was replicated on 500 bootstrap samples.

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. Scores for each outcome were split between RSP and non-RSP. RSP associated to EDSS (n=341) had a HR=0.48 (p=0.001), vs non-RSP with HR=0.89 (p=0.308). RSPs associated to 9HPT (n=403) had a HR=0.52 (p=0.007) and non-RSP HR=1.05 (p=0.751); T25FW RSP (n=905) had a HR=0.74 (p=0.008), vs HR=1.23 (p=0.077) in non-RSP; while SDMT RSP (n=899) had a HR=0.58 (p=0.001) vs HR=1.00 (p=0.988) in non-RSP. Overall, 1290/1645(78%) patients were pronounced siponimod-treatment responders in ≥ one of the 4 clinical outcomes.

Conclusions

This study emphasizes the relevance of evaluating treatment response on different aspects of MS. This methodology allows to depict patient profiles from baseline characteristics that are associated with higher treatment effects on individual outcomes. 78% of SPMS patients had a large treatment benefit with siponimod on at least one of the 4 clinical outcomes.

Authors/Disclosures
Daniela Piani Meier PRESENTER	Daniela Piani Meier has received personal compensation for serving as an employee of Novartis Pharma AG.
	No disclosure on file
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	Dr. Kappos has nothing to disclose.
	No disclosure on file
Goeril Karlsson, PhD	Dr. Karlsson has received personal compensation for serving as an employee of Novartis.
Maria Pia Sormani (University of Genoa)	Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol meyer. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunic. Maria Pia Sormani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis, Roche. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche.

��ɫ��

��ɫ��