Session Information
Date: Thursday, November 14, 2019
Session Title: Research Spotlight: General Rehabilitation
Session Time: 1:30pm-2:15pm
Location: Research Hub - Live Theater
Disclosures: Bruce Cree, MD, PhD, MAS: Abbvie: Consultant/Advisory Board
Akili: Consultant/Advisory Board
Alexion: Consultant/Advisory Board
Biogen: Consultant/Advisory Board
EMD Serono: Consultant/Advisory Board
Novartis: Consultant/Advisory Board
Objective: In EXPAND, siponimod reduced risk of confirmed disability progression (CDP) in patients with secondary progressive multiple sclerosis (SPMS). We assessed the impact of siponimod on CDP in patients with/without relapses to uncouple treatment effects on CDP from those on relapses.
Design: EXPAND was a phase 3 randomized, double-blind, placebo-controlled trial.
Setting: EXPAND was conducted at 292 hospitals and multiple sclerosis centres in 31 countries.
Participants: Patients (aged 18–60 years) with SPMS and Expanded Disability Status Scale score of 3.0–6.5.
Interventions: Once-daily oral fingolimod 2 mg or placebo for up to 3 years.
Main Outcome Measures: We analysed the impact of siponimod on CDP by subgroup analysis using the Cox model on time to 3-month- (m-)/6m-CDP in patients with/without relapses in the 1 and 2 years before study; principal stratum analysis to estimate the effect in patients who would not have relapsed on-study at the m12, m18 and m24 timepoints, regardless of treatment; and Cox model on time to 3m/6m-CDP in the overall population, censoring at time of first relapse.
Results: For non-relapsing patients in 1 and 2 years before study, risk reductions were 18% (HR, 0.82 [CI:0.66;1.02]) and 13% (0.87 [0.68;1.11]) for 3m-CDP, and 25% (0.75 [0.59;0.96]) and 18% (0.82 [0.62;1.08]) for 6m-CDP, respectively; for relapsing patients, risk reductions were 33%/33% (3m-CDP) and 30%/37% (6m-CDP), respectively. In principal stratum estimates, siponimod reduced 3m-CDP by 14–20% and 6m-CDP by 29–33% in non-relapsing patients across the 3 timepoints, suggesting that these patients achieved a large proportion of the effect in the overall population. Cox model censoring at relapse confirmed beneficial effects reaching nominal statistical significance (6m-CDP: HR 0.77 [0.62;0.96]).
Conclusions: Siponimod reduces risk of CDP in SPMS patients with/without relapses, indicating that the effects on disability are largely independent from those on relapses. This abstract has been submitted on behalf of the EXPAND study investigators.
Level of Evidence: Level I
To cite this abstract in AMA style:
Cree B, Fox R, Giovannoni G, Vermersch P, Bar-Or A, Gold R, Rouyrre N, Karlsson G, Dahlke F, Kappos L. Siponimod Affects Disability Progression in Patients with SPMS Independent of Relapse Activity: Results from the Phase 3 EXPAND Study [abstract]. PM R. 2019; 11(S2)(suppl 2). https://pmrjabstracts.org/abstract/siponimod-affects-disability-progression-in-patients-with-spms-independent-of-relapse-activity-results-from-the-phase-3-expand-study/. Accessed May 15, 2025.« Back to AAPM&R Annual Assembly 2019
PM&R Meeting Abstracts - https://pmrjabstracts.org/abstract/siponimod-affects-disability-progression-in-patients-with-spms-independent-of-relapse-activity-results-from-the-phase-3-expand-study/