Effect of siponimod on magnetic resonance imaging measures of neurodegeneration and myelination in secondary progressive multiple sclerosis: Gray matter atrophy and magnetization transfer ratio analyses from the EXPAND phase 3 trial. (September 2022)

• Record Type: Journal Article
• Authors: Arnold, Douglas L; Piani-Meier, Daniela; Bar-Or, Amit; Benedict, Ralph HB; Cree, Bruce AC; Giovannoni, Gavin; Gold, Ralf; Vermersch, Patrick; Arnould, Sophie; Dahlke, Frank; Hach, Thomas; Ritter, Shannon; Karlsson, Göril; Kappos, Ludwig; Fox, Robert J
• Is Part Of: Multiple sclerosis. Volume 28:Number 10(2022)
• Page Start: 1526
• Page End: 1540
• Publication Date: 2022-09
• Subjects: Secondary progressive multiple sclerosis -- MRI -- magnetization transfer ratio -- gray matter -- brain integrity -- myelination -- siponimod; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/13524585221076717
• Languages: English
• ISSNs: 1352-4585

Abstract

Background: Magnetic resonance imaging (MRI) measurements of gray matter (GM) atrophy and magnetization transfer ratio (MTR; correlate of myelination) may provide better insights than conventional MRI regarding brain tissue integrity/myelination in multiple sclerosis (MS). Objective: To examine the effect of siponimod in the EXPAND trial on whole-brain and GM atrophy, newly formed normalized magnetization transfer ratio (nMTR) lesions, and nMTR-assessed integrity of normal-appearing brain tissue (NABT), cortical GM (cGM), and normal-appearing white matter (NAWM). Methods: Patients with secondary progressive multiple sclerosis (SPMS) received siponimod (2 mg/day; n =1037) or placebo ( n = 523). Endpoints included percentage change from baseline to months 12/24 in whole-brain, cGM, and thalamic volumes; change in nMTR from baseline to months 12/24 in NABT, cGM, and NAWM; MTR recovery in newly formed lesions. Results: Compared with placebo, siponimod significantly reduced progression of whole-brain and GM atrophy over 12/24 months, and was associated with improvements in brain tissue integrity/myelination within newly formed nMTR lesions and across NABT, cGM, and NAWM over 24 months. Effects were consistent across age, disease duration, inflammatory activity subgroups, and disease severity. Conclusion: Siponimod reduced brain tissue damage in patients with SPMS as evidenced by objective measures of brain tissue integrity/myelination. This is consistent with central nervous system (CNS) effects observed in preclinical models. ClinicalTrials.gov number: NCT01665144.