Cognitive test performance and disease progression in primary and secondary progressive MS: An analysis of the SPRINT-MS study
- PMID: 40338019
- DOI: 10.1177/13524585251335213
Cognitive test performance and disease progression in primary and secondary progressive MS: An analysis of the SPRINT-MS study
Abstract
Background: Clinical trials of disease-modifying therapies (DMTs) for multiple sclerosis (MS) increasingly incorporate cognitive outcomes, although effects of DMTs on cognition remain unknown.
Methods: In this secondary analysis of data from SPRINT-MS, a phase 2 randomized, placebo-controlled trial of ibudilast for progressive MS, we evaluated performance on Symbol Digit Modalities Test (SDMT) and Selective Reminding Test (SRT) in relation to physical disability, brain volume assessed with magnetic resonance imaging, and retinal nerve fiber layer (RNFL) thickness over 96-week follow-up. We hypothesize that trial participants would show a decline in cognitive test scores over 96 weeks of follow-up, with a possible between-group difference in favor of ibudilast.
Results: Data from 255 participants were analyzed. On average, physical outcome measures, brain parenchymal fraction, and RNFL thickness worsened; average SDMT and SRT scores remained largely unchanged. There were no differences between treatment groups in cognitive outcomes at 96-week follow-up. Practice effects likely contributed to results.
Conclusions: Observed stability of cognitive scores in individuals with progressive MS over 96-week follow-up may reflect true cognitive stability. However, the possibility that current cognitive measurement instruments are psychometrically flawed remains, warranting further research.
Keywords: Clinical trial; cognition; disease-modifying therapies.
Conflict of interest statement
Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Professor V.L. has nothing to declare. Professor R.F. has received personal consulting fees from AB Science, Biogen, Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Immunic, INmune Bio, Janssen, Kiniksa, Lily, Novartis, Sanofi, Siemens, and TG Therapeutics; serves on advisory committees for AB Science, Biogen, Immunic, Janssen, Novartis, and Sanofi, and receives clinical trial contract and research grant funding from Biogen, Novartis, and Sanofi. Dr JM has nothing to declare. Professor M.D. has received consultancy fees, educational support, research grants and/or other forms of financial assistance from Merck, Teva, Biogen, Sanofi Genzyme, Novartis, Roches, Almirall, Janssen-Cilaq, and Bristol-Myers Squibb. Dr E.M. has received honoraria as consultant in advisory boards, and or as chairperson or lecturer in meetings, assistance to congresses and has also participated in clinical trials and other research projects promoted by Almirall, Bayer, Biogen-Idec, Bristol-Myers Squibb, Janssen, Merck-Serono, Teva, Novartis, Roche, Sandoz, and Sanofi Genzyme. Dr L.B.R. has nothing to declare. Dr P.R. has received personal consulting fees from Alexion, Biogen, Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Horizon, Immunic, Novartis, Sanofi, and TG Therapeutics; serves on speaker bureau of Alexion, Amgen, Biogen, Bristol-Myers Squibb, Genentech, and TG Therapeutics, and receives clinical trial contract and research grant funding from Biogen, Bristol-Myers Squibb, and Genentech. Dr J.D.B. has received consulting and speaking fees from Biogen IDEC, Bristol-Myers Squibb, Genentech, Novartis, and TG Therapeutics; clinical trial contract and research grant funding from Biogen, Bristol-Myers Squibb, Genentech, Novartis, Roche, and TG Therapeutics; and has stock ownership in Amgen. Dr J.C. has received consulting honoraria from Novartis and travel support from EDM Serono. Professor B.U. has received consultancy fees from Immunic Therapeutics. Dr E.S. has received speaker fees from Novartis and Merck. Professor G.C. has received compensation from the following Data and Safety Monitoring Boards: Applied Therapeutics, AI therapeutics, AMO Pharma, Argenx, Astra-Zeneca, Avexis Pharmaceuticals, Bristol Meyers Squibb/Celgene, CSL Behring, Cynata Therapeutics, DiameticaTherapeutics, Horizon Pharmaceuticals, Immunic, Inhibrix, Karuna Therapeutics, Kezar Life Sciences, Medtronic, Mapi Pharmaceuticals LTD, Medtronic, Merck, Mitsubishi Tanabe Pharma Holdings, Opko Biologics, Prothena Biosciences, Novartis, Pipeline Therapeutics, Regeneron, Sanofi-Aventis, Reata Pharmaceuticals, Teva Pharmaceuticals, United BioSource LLC, University of Texas Southwestern, University of Pennsylvania, Visioneering Technologies, Inc. Consulting or Advisory Boards: Alexion, Antisense Therapeutics, Avotres, Biogen, Clene Nanomedicine, Clinical Trial Solutions LLC, Endra Life Sciences, Cognito Therapeutics, Entelexo Biotherapeutics, Inc., Genzyme, Genentech, GW Pharmaceuticals, Hoya Corporation, Immunic, Immunosis Pty Ltd, Klein-Buendel Incorporated, Linical, Merck/Serono, Novartis, Perception Neurosciences, Protalix Biotherapeutics, Regeneron, Roche, SAB Biotherapeutics, Sapience Therapeutics, and Scott&Scott LLP. Dr G.C. is employed by the University of Alabama at Birmingham and President of Pythagoras, Inc. a private consulting company located in Birmingham AL. Dr M.W.K. reports advisory boards/consultancy fees and travel support for Biogen, EMD Serono, Roche, Sanofi Genzyme, and Novartis.
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