1. Siponimod vs placebo in active secondary progressive multiple sclerosis: a post hoc analysis from the phase 3 EXPAND study
- Author
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Gold, Ralf, Piani-Meier, Daniela, Kappos, Ludwig, Bar-Or, Amit, Vermersch, Patrick, Giovannoni, Gavin, Fox, Robert J, Arnold, Douglas L, Benedict, Ralph H B, Penner, Iris-Katharina, Rouyrre, Nicolas, Kilaru, Ajay, Karlsson, Göril, Ritter, Shannon, Dahlke, Frank, Hach, Thomas, and Cree, Bruce A C
- Subjects
Multiple Sclerosis ,Clinical Trials and Supportive Activities ,Clinical Sciences ,610 Medicine & health ,Relapsing-Remitting ,Siponimod ,Multiple Sclerosis, Relapsing-Remitting ,Cognition ,Clinical Research ,Benzyl Compounds ,Active secondary progressive multiple sclerosis ,Humans ,Disability progression ,Neurology & Neurosurgery ,Neurosciences ,Evaluation of treatments and therapeutic interventions ,Multiple Sclerosis, Chronic Progressive ,Magnetic Resonance Imaging ,Brain Disorders ,EXPAND ,Chronic Progressive ,Neurology ,6.1 Pharmaceuticals ,Disease Progression ,Azetidines ,Biomedical Imaging ,Neurology (clinical) ,MRI - Abstract
Background Siponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries; however, phase 3 EXPAND study data are from an SPMS population with/without disease activity. A need exists to characterize efficacy/safety of siponimod in aSPMS. Methods Post hoc analysis of participants with aSPMS (≥ 1 relapse in 2 years before study and/or ≥ 1 T1 gadolinium-enhancing [Gd +] magnetic resonance imaging [MRI] lesions at baseline) receiving oral siponimod (2 mg/day) or placebo for up to 3 years in EXPAND. Endpoints: 3-month/6-month confirmed disability progression (3mCDP/6mCDP); 3-month confirmed ≥ 20% worsening in Timed 25-Foot Walk (T25FW); 6-month confirmed improvement/worsening in Symbol Digit Modalities Test (SDMT) scores (≥ 4-point change); T2 lesion volume (T2LV) change from baseline; number of T1 Gd + lesions baseline–month 24; number of new/enlarging (N/E) T2 lesions over all visits. Results Data from 779 participants with aSPMS were analysed. Siponimod reduced risk of 3mCDP/6mCDP vs placebo (by 31%/37%, respectively; p p = 0.007) and reduced risk of 6-month confirmed SDMT worsening (by 27%; p = 0.060). Siponimod was associated with less increase in T2LV (1316.3 vs 13.3 mm3; p p Conclusions In aSPMS, siponimod reduced risk of disability progression and was associated with benefits on cognition and MRI outcomes vs placebo. Trial registration ClinicalTrials.gov number: NCT01665144.
- Published
- 2022