Relapse-associated Worsening and Progression-independent Relapse Activity in Ozanimod-treated Participants with Relapsing Multiple Sclerosis from the RADIANCE and DAYBREAK Trials
Massimo Filippi1, Jon Riolo2, Jeffrey Cohen3, Hans-Peter Hartung4, Xavier Montalban5, Sven Meuth6, Leorah Freeman7, Tanuja Chitnis8, Cristina Granziera9, Erik Deboer2, Chun-Yen Cheng2, Jennifer Reardon2, Chahin Pachai2, James Sheffield2, Bruce Cree10, Ludwig Kappos11
1Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute, and Vita-Salute San Raffaele University, Milan, Italy, 2Bristol Myers Squibb, Princeton, New Jersey, USA, 3Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio, USA, 4Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Brain and Mind Centre, University of Sydney, Sydney, Australia; Department of Neurology, Medical University of Vienna, Vienna, Austria; and Palacký University Olomouc, Olomouc, Czech Republic, 5Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain, 6Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany, 7Dell Medical School, The University of Texas at Austin, Austin, Texas, USA, 8Brigham and Women’s Hospital, and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA, 9Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital Basel, Switzerland; 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, 10Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California, USA, 11Research 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
Objective:
To determine the incidence and predictors of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) in participants treated with ozanimod.
Background:
Ozanimod was associated with significantly fewer relapses than interferon beta-1a (IFN) in phase 3 relapsing multiple sclerosis (RMS) trials and provided sustained control of disability progression over 5 years in an open-label extension (OLE) study.
Design/Methods:
Participants treated with ozanimod 0.46mg/d or 0.92mg/d or IFN 30μg/wk for 24 months in the phase 3 RADIANCE trial (NCT02047734) were eligible to enroll in an ozanimod 0.92mg OLE study (DAYBREAK‒NCT02576717; data cutoff: 1 February 2022). Confirmed disability progression ([CDP]; ≥1-point increase in Expanded Disability Status Scale [EDSS] score from baseline, confirmed after 6 months) incidence was determined. RAW and PIRA were defined as previously described (Lublin et al., 2022). Kaplan-Meier analyses and univariable Cox proportional hazards regression were performed.
Results:
363 participants who received continuous ozanimod and 346 who switched from IFN were included. In up to 8 years of follow-up, 75.9% of participants were free of 6-month CDP. Among participants with CDP, 44.3% and 54.5% of those treated with continuous ozanimod had RAW or PIRA, respectively, and 8% had both; 57.8% and 43.4% who switched from IFN to ozanimod had RAW or PIRA, respectively, and 4.8% had both. RAW was observed in 10.7% of participants treated with continuous ozanimod and in 13.9% who switched from IFN to ozanimod; PIRA was observed in 13.2% of participants treated with continuous ozanimod and in 10.4% who switched from IFN to ozanimod. In both treatment groups, nominally significant predictors of RAW included RADIANCE baseline EDSS score (positive association) and whole brain, cortical grey matter, and thalamic volumes (negative associations); these variables were not predictors of PIRA.
Conclusions:
In ozanimod-treated participants with RMS, RAW and PIRA contributed similarly to disability progression over 8 years.