118  Sustained reduction of disability and cognitive decline with long-term siponimod in EXPAND active SPMS patients

Abstract

BackgroundIn the EXPAND study, patients with active SPMS (aSPMS) demonstrated a reduced risk of 3/6-month confirmed disability progression (3m/6m CDP) and risk of decline in cognitive processing speed (CPS, 6-month confirmed cognition worsening of ≥4-point on Symbol Digit Modalities Test [6mCCW]) versus placebo.ObjectivesAssess long-term efficacy and safety of siponimod in patients with aSPMS.MethodsIn aSPMS patients who entered the EXPAND Extension, time to 3m/6mCDP, 6mCCW, and annu- alized relapse rate (ARR) were assessed for the Continuous (siponimod in Core and Extension) and Switch (placebo in Core and open-label siponimod in Core/Extension) groups.ResultsRisk of 6mCDP was reduced by 29% (0.71 [0.57–0.90]; p=0.0044) for Continuous versus Switch group, corresponding to approximately 70% delay in time to 6mCDP. The risk of 6mCCW for Continuous versus Switch group was reduced by 33% (0.67 [0.53–0.86]); p=0.0018), corresponding to approximately 70% delay in time to 6mCCW. A significant reduction in ARR for the Continuous versus Switch groups was observed in patients with or without active disease.ConclusionsLong-term data analyses showed that siponimod effects on disability, cognitive processing speed, and relapse outcomes in patients with active SPMS are sustained up to 5 years, and highlight the value of early treatment initiation.teresa.sawtell@novartis.com

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“…In the preclinical models it was shown to promote remyelination, as S1P receptors are also expressed by oligodendrocytes, neurons, microglia and astrocytes ( 62 ). In the EXPAND Core Study siponimod significantly reduced the risk of a meaningful worsening in the cognitive processing speed [defined as ≥4point decline in the SDMT score] versus placebo ( 63 ).…”