Siponimod and Cognition in Secondary Progressive Multiple Sclerosis: EXPAND Secondary Analyses
Ralph H B Benedict1, Davorka Tomic2, Bruce A Cree2
1From the Department of Neurology (R.H.B.B.), University at Buffalo, NY; Novartis Pharma AG (D.T., H.P., G.K., F.D.), Basel, Switzerland; Weill Institute for Neurosciences (B.A.C.), Department of Neurology, University of California San Francisco; Mellen Center for Treatment and Research in Multiple Sclerosis (R.F.), Neurological Institute, Cleveland Clinic, OH; Blizard Institute (GG), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK; Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef-Hospital/Ruhr-University Bochum, Germany; Department of Neurology (P.V.), University of Lille, INSERM U1172, CHU Lille, FHU Imminent, France; Novartis Ireland Ltd (I.W.), Dublin; Lycalis sprl (C.W.), Brussels, Belgium; and Neurologic Clinic and Policlinic (G.K., L.K.), Departments of Medicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital and University of Basel, Switzerland. benedict@buffalo.edu.
Objective:
To investigate the effects of siponimod on cognitive processing speed in patients with secondary progressive (SP) multiple sclerosis (MS), by means of a predefined exploratory and post hoc analysis of the Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND) study, a randomized controlled trial comparing siponimod and placebo.
Methods:
EXPAND was a double-blind, placebo-controlled phase 3 trial involving 1,651 patients with SPMS randomized (2:1) to either siponimod 2 mg/d or placebo. Cognitive function was assessed with the Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Brief Visuospatial Memory Test-Revised (BVMT-R) administered at baseline, 6-month intervals, and end of treatment.
Results:
Between-group differences in mean change from baseline in SDMT scores were significantly better in siponimod- vs placebo-treated patients at month 12 (difference 1.08 [95% confidence interval 0.23-1.94]; p = 0.0132), month 18 (1.23 [0.25-2.21); p = 0.0135), and month 24 (2.30 [1.11-3.50]; p = 0.0002). Siponimod-treated patients were at significantly lower risk for having a 4-point sustained decrease in SDMT score (hazard ratio [HR] 0.79 [0.65-0.96]; p = 0.0157), while their chance for having a 4-point sustained increase in SDMT score was higher (HR 1.28 [1.05-1.55]; p = 0.0131). PASAT and BVMT-R scores did not differ significantly between the 2 treatment groups (all p > 0.28).
Conclusion:
Siponimod had a significant benefit on SDMT in patients with SPMS. Siponimod-treated patients were at significantly lower risk for having a ≥4-point decrease in SDMT score and had a significantly higher chance for having a ≥4-point increase in SDMT score, a magnitude of change accepted as clinically meaningful.
Clinicaltrialsgov Identifier:
NCT01665144.
Classification Of Evidence:
This study provides Class II evidence that, for patients with SPMS, siponimod had a significant benefit on cognitive processing speed.
More Related Videos
Related Concept Videos
01:30Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
01:27Pharmacodynamics in Geriatric Patients: Effects of Age
01:29Therapeutic Drug Monitoring: Affecting Factors