115 Impact of siponimod on myelination across SPMS subgroups: post-hoc analysis from EXPAND MRI substudy

Abstract

BackgroundChanges 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.ObjectivesInvestigate the effect of siponimod on MTR changes in SPMS subgroups.MethodsThis 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.ResultsThere 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).ConclusionsOver 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.teresa.sawtell@novartis.com