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.
Siponimod significantly improved cognitive processing speed in patients with secondary progressive multiple sclerosis (SPMS), as measured by the Symbol Digit Modalities Test (SDMT). This treatment reduced the risk of cognitive decline and increased the likelihood of cognitive improvement in SPMS patients.
Area of Science:
- Neurology
- Clinical Trials
- Neuroimmunology
Background:
- Secondary progressive multiple sclerosis (SPMS) is characterized by accumulating neurological disability and cognitive impairment.
- Cognitive processing speed is a key domain affected in SPMS, impacting daily functioning.
- Siponimod is an oral sphingosine-1-phosphate receptor modulator approved for SPMS treatment.
Purpose of the Study:
- To evaluate the efficacy of siponimod in improving cognitive processing speed in patients with SPMS.
- To analyze the effects of siponimod on specific cognitive tests, including the Symbol Digit Modalities Test (SDMT).
Main Methods:
- A predefined exploratory and post hoc analysis of the randomized, double-blind, placebo-controlled EXPAND phase 3 trial.
- 1,651 SPMS patients were randomized to siponimod 2 mg/d or placebo.
- Cognitive function assessed using SDMT, PASAT, and BVMT-R at baseline and regular intervals.
Main Results:
- Siponimod treatment resulted in significantly better mean change from baseline in SDMT scores at 12, 18, and 24 months compared to placebo.
- Siponimod-treated patients had a significantly lower risk of a sustained 4-point decrease in SDMT score.
- Siponimod-treated patients had a significantly higher chance of a sustained 4-point increase in SDMT score; PASAT and BVMT-R showed no significant differences.
Conclusions:
- Siponimod demonstrated a significant benefit on cognitive processing speed in patients with SPMS.
- The observed improvements in SDMT scores are considered clinically meaningful.
- Siponimod effectively reduced the risk of cognitive decline and enhanced the potential for cognitive improvement in SPMS patients.
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