Ralph H B Benedict1, Davorka Tomic2, Bruce A Cree2, Robert Fox2, Gavin Giovannoni2, Amit Bar-Or2, Ralf Gold2, Patrick Vermersch2, Harald Pohlmann2, Ian Wright2, Göril Karlsson2, Frank Dahlke2, Christian Wolf2, Ludwig Kappos2. 1. From 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. 2. From 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.
Abstract
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 eithersiponimod 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.
RCT Entities:
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.
Authors: E Doering; M C Hoenig; G N Bischof; K P Bohn; L M Ellingsen; T van Eimeren; A Drzezga Journal: Eur J Nucl Med Mol Imaging Date: 2022-07-14 Impact factor: 10.057
Authors: Ezzat Hashemi; Ezra Yoseph; Hsing-Chuan Tsai; Monica Moreno; Li-Hao Yeh; Shalin B Mehta; Mari Kono; Richard Proia; May H Han Journal: Cell Mol Neurobiol Date: 2022-08-02 Impact factor: 4.231