Effect of Ozanimod on Symbol Digit Modalities Test Performance in Relapsing MS.
Brain volume
Cognition
Multiple sclerosis
Neuropsychological tests
Ozanimod
Journal
Multiple sclerosis and related disorders
ISSN: 2211-0356
Titre abrégé: Mult Scler Relat Disord
Pays: Netherlands
ID NLM: 101580247
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
05
08
2020
revised:
18
11
2020
accepted:
02
12
2020
pubmed:
18
1
2021
medline:
15
5
2021
entrez:
17
1
2021
Statut:
ppublish
Résumé
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). 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. 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. 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).
Sections du résumé
BACKGROUND
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
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
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
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).
Identifiants
pubmed: 33454584
pii: S2211-0348(20)30747-1
doi: 10.1016/j.msard.2020.102673
pii:
doi:
Substances chimiques
Indans
0
Oxadiazoles
0
Interferon beta-1a
XRO4566Q4R
ozanimod
Z80293URPV
Banques de données
ClinicalTrials.gov
['NCT02294058']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
102673Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.