In:
Multiple Sclerosis Journal, SAGE Publications, Vol. 28, No. 10 ( 2022-09), p. 1526-1540
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1352-4585
,
1477-0970
DOI:
10.1177/13524585221076717
Language:
English
Publisher:
SAGE Publications
Publication Date:
2022
detail.hit.zdb_id:
2008225-3
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