1. Effect of Ozanimod on Symbol Digit Modalities Test Performance in Relapsing MS
- Author
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DeLuca, John, Schippling, Sven, Montalban, Xavier, Kappos, Ludwig, Cree, Bruce A.C., Comi, Giancarlo, Arnold, Douglas Lorne, Hartung, Hans Peter, Sheffield, James K., Liu, Hongjuan, Silva, Diego, Cohen, Jeffrey A., Universitat Autònoma de Barcelona. Departament de Medicina, Institut Català de la Salut, [DeLuca J] Kessler Foundation, NJ 07052, USA. Departments of Physical Medicine and Rehabilitation, and Neurology, Rutgers - New Jersey Medical School, Newark 07103, NJ, USA. [Schippling S] Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital and University of Zürich and Neuroscience Center Zürich, University of Zürich, 8091 Zurich, Switzerland. Federal Institute of Technology (ETH) Zürich, 8092 Zürich, Switzerland. [Montalban X] Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Kappos L] Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Medicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital and University of Basel, CH-4031 Basel, Switzerland. [Cree BAC] Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA 94158 USA. [Comi G] Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy, and Vall d'Hebron Barcelona Hospital Campus
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Adult ,medicine.medical_specialty ,Multiple Sclerosis ,Post hoc ,Adolescent ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Neuropsychological Tests ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Multiple sclerosis ,03 medical and health sciences ,Ozanimod ,Young Adult ,0302 clinical medicine ,Cognition ,Multiple Sclerosis, Relapsing-Remitting ,Internal medicine ,medicine ,Humans ,Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis::Multiple Sclerosis, Relapsing-Remitting [DISEASES] ,030212 general & internal medicine ,disciplinas y actividades conductuales::pruebas psicológicas::pruebas neuropsicológicas [PSIQUIATRÍA Y PSICOLOGÍA] ,Beneficial effects ,Tests neuropsicològics ,Behavioral Disciplines and Activities::Psychological Tests::Neuropsychological Tests [PSYCHIATRY AND PSYCHOLOGY] ,Oxadiazoles ,Routine screening ,Brain volume ,medicine.diagnostic_test ,business.industry ,Symbol digit modalities test ,Magnetic resonance imaging ,General Medicine ,Middle Aged ,medicine.disease ,enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple::esclerosis múltiple recurrente-remitente [ENFERMEDADES] ,Brain volume loss ,Clinical trial ,Neurology ,Neuropsychological tests ,Indans ,Neurology (clinical) ,business ,Esclerosi múltiple - Tractament ,030217 neurology & neurosurgery ,Interferon beta-1a - Abstract
Brain volume; Multiple sclerosis; Ozanimod Volumen cerebral; Esclerosis múltiple; Ozanimod Volum cerebral; Esclerosi múltiple; Ozanimod Background Cognitive dysfunction, including slowed cognitive processing speed (CPS), is one of the most disabling symptoms of multiple sclerosis (MS). The Symbol Digit Modalities Test (SDMT) is a preferred measure of CPS for MS trials and routine screening. Based on encouraging SDMT results in the phase 3 SUNBEAM trial, these post hoc, exploratory analyses were conducted to further compare effects of the sphingosine 1-phosphate receptor modulator ozanimod versus intramuscular interferon β-1a on CPS in participants with relapsing multiple sclerosis (RMS). Methods In the phase 3, double-blind, double-dummy, SUNBEAM study, adults (aged 18‒55 years) with RMS (N=1,346) were randomized to once-daily oral ozanimod 0.92 or 0.46 mg, or weekly intramuscular interferon β-1a 30 µg. The study continued until the last participant was treated for 12 months. CPS was measured as part of a secondary endpoint using the SDMT. Exploratory, post hoc analyses evaluated SDMT change and percentages of participants with clinically meaningful (≥4-point) SDMT improvement or worsening at months 6 and 12, and relationship between SDMT and brain volume on magnetic resonance imaging. Results Ozanimod improved SDMT scores compared with interferon β-1a at months 6 and 12. At month 12, least squares mean difference in SDMT z-scores for ozanimod 0.92 mg versus interferon β-1a was 0.102 (95% CI, 0.031‒0.174, nominal p = 0.0051; standardized mean difference = 0.1376). A greater percentage of ozanimod 0.92 mg‒treated participants had clinically meaningful improvements in SDMT scores versus interferon β-1a at month 6 (30.0% versus 22.2%) and month 12 (35.6% versus 27.9%). Of those with SDMT improvement at month 6, 66.4% of those treated with ozanimod 0.92 mg and 55.9% of those treated with interferon β-1a had sustained improvement at month 12. Brain volume loss was similar for those with SDMT improvement versus worsening at month 12. Conclusions In these exploratory analyses, ozanimod had modestly beneficial effects on CPS in RMS participants. The effects of ozanimod on SDMT are being further evaluated in an ongoing 3-year clinical trial. SUNBEAM is registered on clinicaltrials.gov (NCT02294058) and the European Clinical Trials Database (EudraCT 2014‐002320‐27). SUNBEAM was sponsored by Celgene Corporation. The sponsor was involved in data analysis and interpretation, and manuscript preparation, review, and approval. All authors vouch for data accuracy, reviewed all drafts, and approved the final manuscript.
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- 2020