Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Up to 5 years of follow-up in the DAYBREAK open-label extension trial

Author:

Cree Bruce AC1ORCID,Selmaj Krzysztof W2,Steinman Lawrence3,Comi Giancarlo4,Bar-Or Amit5,Arnold Douglas L6ORCID,Hartung Hans-Peter7,Montalbán Xavier8,Havrdová Eva K9,Sheffield James K10,Minton Neil10,Cheng Chun-Yen10,Silva Diego10,Kappos Ludwig11ORCID,Cohen Jeffrey A12ORCID

Affiliation:

1. Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA

2. Center for Neurology, Łódź, Poland and Collegium Medicum, Department of Neurology, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland

3. Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, CA, USA

4. Vita-Salute San Raffaele University and Casa di Cura del Policlinico, Milan, Italy

5. Center for Neuroinflammation and Experimental Therapeutics, and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

6. NeuroRx Research and Montréal Neurological Institute, McGill University, Montréal, QC, Canada

7. Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany/Brain and Mind Centre, The University of Sydney, Sydney, Australia/Department of Neurology, Medical University of Vienna, Vienna, Austria/Department of Neurology, Palacky University Olomouc, Olomouc, Czech Republic

8. Department of Neurology-Neuroimmunology, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d’Hebron, Barcelona, Spain

9. Department of Neurology and Center for Clinical Neuroscience, First Medical Faculty, Charles University, Prague, Czech Republic

10. Bristol Myers Squibb, Princeton, NJ, USA

11. Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Head, Spine and Neuromedicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland

12. Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, OH, USA

Abstract

Background: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for treatment of relapsing forms of MS. Objective: To characterize long-term safety and efficacy of ozanimod. Methods: Patients with relapsing MS who completed a phase 1‒3 ozanimod trial were eligible for an open-label extension study (DAYBREAK) of ozanimod 0.92 mg/d. DAYBREAK began 16 October 2015; cutoff for this interim analysis was 2 February 2021. Results: This analysis included 2494 participants with mean 46.8 (SD 11.9; range 0.033‒62.7) months of ozanimod exposure in DAYBREAK. During DAYBREAK, 2143 patients (85.9%) had treatment-emergent adverse events (TEAEs; similar in nature to those in the parent trials), 298 (11.9%) had a serious TEAE, and 75 (3.0%) discontinued treatment due to TEAEs. Serious infections (2.8%), herpes zoster infections (1.7%), confirmed macular edema cases (0.2%), and cardiac TEAEs (2.8%) were infrequent. Adjusted annualized relapse rate was 0.103 (95% confidence interval, 0.086‒0.123). Over 48 months, 71% of patients remained relapse free. Adjusted mean numbers of new/enlarging T2 lesions/scan and gadolinium-enhancing lesions were low and similar across parent trial treatment subgroups. Conclusions: This long-term extension of ozanimod trials confirmed a favorable safety/tolerability profile and sustained benefit on clinical and magnetic resonance imaging measures of disease activity.

Funder

Celgene International II

Publisher

SAGE Publications

Subject

Neurology (clinical),Neurology

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