115  Impact of siponimod on myelination across SPMS subgroups: post-hoc analysis from EXPAND MRI substudy. Issue 6 (27th May 2022)

• Record Type: Journal Article
• Authors: Arnold, DL; Bar-Or, A; Cree, BAC; Giovannoni, G; Gold, R; Vermersch, P; Piani-Meier, D; Arnould, S; Kappos, L
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 93:Issue 6(2022)
• Page Start: A137
• Page End: A137
• Publication Date: 2022-05-27
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2022-ABN.440
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Background: Changes in magnetization transfer ratio (MTR) are a marker of changes in myelin density and brain tissue integrity. Siponimod improved lesional MTR recovery in the overall EXPAND secondary progressive multiple sclerosis (SPMS) population. Objectives: Investigate the effect of siponimod on MTR changes in SPMS subgroups. Methods: This prospective sub-study assessed the effect of siponimod versus placebo on median nor- malized MTR (nMTR) in normal appearing brain tissue (NABT), cortical Grey Matter (cGM) and normal appearing white matter (NAWM). Subgroups were defined by: disease history, severity and duration, EDSS score, Symbol Digit Modalities Test score, and inflammatory disease activity. Results: There was an attenuation in median nMTR decrease versus placebo across all subgroups (all p<0.05 except EDSS≥6 subgroup, p=0.064). In the active SPMS subgroup, siponimod attenuated median nMTR decrease across NABT, cGM and NAWM by 91–109% (p<0.01 all); and in the non-active SPMS subgroup by 170– 198% (p=0.0151 for NAWM, p>0.05 for NABT, cGM). Conclusions: Over 24 months, siponimod attenuated the decrease in median nMTR in brain tissues across patient subgroups characterized by disease activity and severity, with most pronounced effects in NAWM. This supports preclinical studies, showing beneficial CNS effects on myelination. [e-mail]