Correlations Between Early MRI Parameters and Long-term Clinical Outcomes in Phase 3 and Open-label Extension Studies of Ozanimod in Relapsing Multiple Sclerosis
Douglas L. Arnold1, Leorah Freeman2, Hans-Peter Hartung3, Xavier Montalbán4, Jeffrey A. Cohen5, Amit Bar-Or6, Lawrence Steinman7, John DeLuca8, Chun-Yen Cheng9, Jon V. Riolo9, Diego Silva9, Chahin Pachai9, Bruce A. C. Cree10
1NeuroRx Research and Montréal Neurological Institute, McGill University, Montréal, Quebec, Canada, 2Dell Medical School, The University of Texas at Austin, Austin, Texas, 3Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Brain and Mind Centre, University of Sydney, Australia; Department of Neurology, Medical University of Vienna, Austria; and Palacký University Olomouc, Olomouc, Czech Republic, 4Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain, 5Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio, 6Center for Neuroinflammation and Experimental Therapeutics, and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 7Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, California, 8Kessler Foundation, West Orange, New Jersey, and Departments of Physical Medicine and Rehabilitation, and Neurology, Rutgers - New Jersey Medical School, Newark, New Jersey, 9Bristol Myers Squibb, Princeton, New Jersey, 10Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California
Objective:
To explore correlations between early MRI parameters and long-term clinical outcomes in patients with relapsing multiple sclerosis (RMS).
Background:
The ability of early MRI parameters to predict long-term clinical outcomes of RMS is not clear.
Design/Methods:
This post-hoc analysis pooled data from patients treated with ozanimod 0.92 mg/d in phase 3 SUNBEAM (NCT02294058) and RADIANCE (NCT02047734) who entered the DAYBREAK open-label extension (OLE) (NCT02576717), in which all patients received ozanimod 0.92 mg/d. Early MRI parameters included observed (baseline [BL]) and % change in (month 12 [M12]) whole brain volume (WBV), thalamic volume (TV), and cortical grey matter volume; BL and M12 gadolinium-enhancing (GdE) lesion count and T1 and T2 lesion volumes; and M12 new/enlarging T2 lesion count. Outcomes included number of relapses in the OLE, cognitive processing speed (Symbol Digit Modalities Test [SDMT]), and disability (Expanded Disability Status Scale [EDSS]) at OLE month 48 (M48).
Results:
Of the BL MRI outcomes, SDMT scores at OLE M48 correlated most strongly (ρ>0.46‒<0.49) with T1 lesion volume (inverse correlation) and TV; EDSS at OLE M48 correlated less strongly with these MRI parameters (ρ>0.38‒<0.42). For EDSS scores at OLE M48, the strongest correlations (ρ>0.41‒<0.42) were observed with BL TV and WBV (inverse correlations). SDMT and EDSS correlated poorly with BL GdE lesion count (ρ<0.11). Of the M12 MRI outcomes, SDMT and EDSS scores correlated most strongly with T1 and T2 lesion volumes (SDMT, ρ>0.44‒<0.50, inverse correlations; EDSS scores, ρ>0.34‒<0.39). Relapses during the OLE were poorly correlated with BL and M12 MRI parameters (ρ<0.19).
Conclusions:
MRI lesion volumes and TV had stronger correlations with SDMT than with EDSS long term, suggesting MRI measures may be better predictors of cognition than physical disability over the long term. These results may be used to improve predictive models of clinical outcomes and treatment response in RMS.