Brain Volume Changes Over 1 Year in Ozanimod-treated Patients with Early-relapsing Multiple Sclerosis: An Interim Analysis of the ENLIGHTEN Study
Robert Zivadinov1, Robert Naismith2, Sarah Morrow3, Ann Bass4, Ahmed Obeidat5, Emily Riser6, Sibyl Wray7, Jon Riolo8, Burhan Chaudhry8, Andrew Thorpe8, Chun-Yen Cheng8, John DeLuca9
1Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York, 2Washington University School of Medicine, St Louis, Missouri, 3London Health Sciences Centre, University Hospital, University of Western Ontario, London, Ontario, Canada, and Department of Clinical Neurological Sciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada, 4Neurology Center of San Antonio, San Antonio, Texas, 5Medical College of Wisconsin, Milwaukee, Wisconsin, 6Alabama Neurology Associates, Birmingham, Alabama, 7Hope Neurology MS Center, Knoxville, Tennessee, 8Bristol Myers Squibb, Princeton, New Jersey, 9Kessler Foundation, West Orange, New Jersey, and Departments of Physical Medicine and Rehabilitation, and Neurology, Rutgers - New Jersey Medical School, Newark, New Jersey
Objective:
To report brain volume changes over 1 year in ENLIGHTEN participants.
Background:
Whole brain volume (WBV) declines with normal aging (−0.28%/y). Patients with multiple sclerosis (MS) often have accelerated WBV loss.
Design/Methods:
ENLIGHTEN (NCT04140305) is an open-label study of ozanimod 0.92 mg in patients with early relapsing MS. Percent change in brain volumes over 1 year are analyzed using SIENA (for WBV), FreeSurfer (for thalamic volume [TV] and medulla oblongata volume [MOV]), a modified hybrid of SIENA and SIENAX methods (mSIENAX-multi time point for cortical grey matter volume [CGMV]), SIENAX (for baseline lateral ventricle volume [LVV]) and VIENA on 3-dimensional T1-weighted image (for 1-year LVV). Least squares (LS) means and 95% confidence intervals (CIs) are generated for the percent changes from baseline using a mixed-effect model with repeated measures adjusted for baseline volume and age.
Results:
A total of 185 patients with a mean (standard deviation [SD]) age of 39.5 (10.7) years were enrolled at data cutoff (02/14/2023) and received ≥1 ozanimod dose; most were White (159; 85.9%), female (145; 78.4%), and DMT-naive (134; 72.4%). Mean (SD) baseline (n=184) brain volume (cm3) and mean (SD) percent change at year 1, respectively, were 1510.4 (130.2) and −0.28% (0.76) for WBV (n=98); 16.2 (1.9) and 0.07% (4.50) for TV (n=97); 619.0 (75.9) and 0.63% (2.13) for CGMV (n=97); 5.9 (0.8) and 0.35% (7.25) for MOV (n=98); and 39.6 (14.7) and 1.16% (7.76) for LVV (n=98). LS mean (95% CI) percent change was −0.28% (−0.43, −0.12) for WBV; 0.07% (−0.82, 0.97) for TV; 0.63% (0.21, 1.06) for CGMV; 0.35% (−0.98, 1.67) for MOV; and 1.14% (−0.38, 2.67) for LVV.
Conclusions:
In ENLIGHTEN participants, WBV decreased at a rate consistent with healthy controls. TV, CGMV, and MOV did not decrease significantly, and LVV did not increase significantly, suggesting preservation of these structures.