@article{0ca8ae19bf194876a1e97b954c262d30,
title = "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",
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.",
keywords = "adverse events, clinical efficacy, extension study, Multiple sclerosis, ozanimod, sphingosine 1-phosphate receptor modulators",
author = "Cree, {Bruce A.C.} and Selmaj, {Krzysztof W.} and Lawrence Steinman and Giancarlo Comi and Amit Bar-Or and Arnold, {Douglas L.} and Hartung, {Hans Peter} and Xavier Montalb{\'a}n and Havrdov{\'a}, {Eva K.} and Sheffield, {James K.} and Neil Minton and Cheng, {Chun Yen} and Diego Silva and Ludwig Kappos and Cohen, {Jeffrey A.}",
note = "Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: B.A.C.C. reports personal compensation for consulting for Alexion, Atara, Autobahn, Avotres, Biogen, EMD Serono, Gossamer Bio, Horizon, Neuron23, Novartis, Sanofi, TG Therapeutics, and Therini, and received research support from Genentech. K.W.S. reports consulting for Biogen, Celgene, Genzyme, Merck, Novartis, Ono Pharma, Roche, Synthon, and Teva. L.S. reports consulting for AbbVie, Atreca, Celgene, Novartis, Teva, Tolerion, and EMD Serono, and research support from Atara, Biogen, and Celgene. G.C. reports compensation for consulting and/or speaking activities from Almirall, Biogen, Celgene, EXCEMED, Forward Pharma, Genzyme, Merck, Novartis, Roche, Sanofi, and Teva. A.B.-O. participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from Atara Biotherapeutics, Biogen, BMS-Celgene, EMD Serono, Sanofi-Genzyme, Novartis, and Roche-Genentech. D.L.A. reports personal fees for consulting and/or grants from Albert Charitable Trust, Biogen, Novartis, Celgene, F. Hoffmann-La Roche, Frequency Therapeutics, MedDay, Merck Serono, Novartis, Population Council, and Sanofi-Aventis; grants from Biogen, Immunotec, and Novartis; and an equity interest in NeuroRx Research. H.-P.H. reports personal fees for consulting, serving on steering committees, and speaking from Bayer Healthcare, Biogen, Celgene, GeNeuro, Genzyme, Merck, MedImmune, Novartis, Octapharma, Roche, Sanofi, and Teva. X.M. has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past 3 years with Actelion, Alexion, Bayer, Biogen, Bristol Myers Squibb/Celgene, EMD Serono, EXCEMED, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, MedDay, Merck, Mylan, MSIF, Nervgen, NMSS, Novartis, Roche, Sanofi-Genzyme, Teva Pharmaceuticals, and TG Therapeutics. E.K.H. reports personal compensation for consulting and speaking for Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi, and Teva, and is supported by Czech Ministry of Education, project PROGRES Q27/LF1. J.K.S., N.M. C.-Y.C and D.S. are employees and shareholders of Bristol Myers Squibb. L.K. has received institutional research support: steering committee, advisory board, consultancy fees: Actelion, Bayer HealthCare, Biogen, Bristol Myers Squibb, Genzyme, Janssen, Japan Tobacco, Merck, Novartis, Roche, Sanofi, Santhera, Shionogi, and TG therapeutics; speaker fees: Bayer HealthCare, Biogen, Merck, Novartis, Roche, and Sanofi; support of educational activities: Allergan, Bayer HealthCare, Biogen, CSL Behring, Desitin, Genzyme, Merck, Novartis, Roche, Pfizer, Sanofi, Shire, and Teva; license fees for Neurostatus products; and grants: Bayer HealthCare, Biogen, European Union, Innosuisse, Merck, Novartis, Roche, Swiss MS Society, and Swiss National Research Foundation. J.A.C. reports personal compensation for consulting for Adamas, Atara, Bristol Myers Squibb, Convelo, MedDay, and Mylan; and serving as an Editor of Multiple Sclerosis Journal. Funding Information: Support for third-party writing assistance for this manuscript was provided by Lauren A Cerruto and Jessica D Herr, PharmD, of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb. The authors thank Sonia Ariana Afsari, MD, and Jenna Hoogerheyde for reviewing the manuscript and also thank the members of the Data Monitoring Committee, the Macular Edema Review Panel, the expert hepatic safety advisors, the patients, their families, and trial investigators for their contributions. Publisher Copyright: {\textcopyright} The Author(s), 2022.",
year = "2022",
month = oct,
doi = "10.1177/13524585221102584",
language = "English",
volume = "28",
pages = "1944--1962",
journal = "Multiple Sclerosis Journal",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "12",
}