Siponimod vs placebo in active secondary progressive multiple sclerosis: a post hoc analysis from the phase 3 EXPAND study

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...

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Published in:Journal of neurology Vol. 269; no. 9; pp. 5093 - 5104
Main Authors: 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, Cree, Bruce A. C.
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2022
Springer Nature B.V
Subjects:
Azetidines - pharmacology
Azetidines - therapeutic use
Benzyl Compounds - pharmacology
Benzyl Compounds - therapeutic use
Cognition
Disease Progression
Gadolinium
Humans
Lesions
Magnetic Resonance Imaging
Medicine
Medicine & Public Health
Multiple sclerosis
Multiple Sclerosis - drug therapy
Multiple Sclerosis, Chronic Progressive - diagnostic imaging
Multiple Sclerosis, Chronic Progressive - drug therapy
Multiple Sclerosis, Relapsing-Remitting - drug therapy
NCT
NCT01665144
Neurology
Neuroradiology
Neurosciences
Original Communication
Placebos
Sphingosine 1-phosphate
EXPAND
Active secondary progressive multiple sclerosis
Disability progression
Cognition
Siponimod
MRI
ISSN:0340-5354, 1432-1459, 1432-1459
Online Access:Get full text
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Summary: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  < 0.01); there was no significant effect on T25FW. Siponimod increased likelihood of 6-month confirmed SDMT improvement vs placebo (by 62%; 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 mm 3 ; p  < 0.0001), and fewer T1 Gd + and N/E T2 lesions than placebo (85% and 80% reductions, respectively; p  < 0.0001). 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.
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ISSN:0340-5354
1432-1459
1432-1459
DOI:10.1007/s00415-022-11166-z