Effect of Ozanimod on Symbol Digit Modalities Test Performance in Relapsing MS
DeLuca, John (Rutgers - The State University of New Jersey, Newark)
Schippling, Sven (University of Zurich)
Montalban, Xavier (Hospital Universitari Vall d'Hebron)
Kappos, Ludwig (University of Basel)
Cree, Bruce A. C (University of California, San Francisco)
Comi, Giancarlo (Vita-Salute San Raffaele University)
Arnold, Douglas Lorne (McGill University, Montreal)
Hartung, Hans Peter (Heinrich Heine University Düsseldorf)
Sheffield, James K. (Bristol-Myers Squibb Company)
Liu, Hongjuan (Bristol-Myers Squibb Company)
Silva, Diego (Bristol-Myers Squibb Company)
Cohen, Jeffrey A. (Neurological Institute, Cleveland Clinic)
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2021
Resum:	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).
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Brain volume ; Cognition ; Multiple sclerosis ; Neuropsychological tests ; Ozanimod
Publicat a:	Multiple Sclerosis and Related Disorders, Vol. 48 (2021) , p. 102673, ISSN 2211-0356

DOI: 10.1016/j.msard.2020.102673
PMID: 33454584

9 p, 2.2 MB

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