2023 American Academy of Neurology Abstract Website

Bruce A. C. Cree¹, Rachel Maddux², Amit Bar-Or³, Hans-Peter Hartung⁴, Amandeep Kaur², Elizabeth Brown², Sarah Hu², James Sheffield², Diego Silva², Sarah Harris²
¹Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California, ²Bristol Myers Squibb, Princeton, New Jersey, ³Center for Neuroinflammation and Experimental Therapeutics, and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 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

Objective:

To describe the serological response and clinical outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination in ozanimod-treated participants with relapsing multiple sclerosis (RMS) in an open-label extension (OLE) trial.

Background:

Multiple sclerosis disease-modifying therapies, including sphingosine 1-phosphate receptor modulators, may attenuate the response to SARS-CoV-2 infection or vaccination.

Design/Methods:

Participants with RMS who completed a phase 1‒3 ozanimod trial could enter an OLE trial (DAYBREAK‒NCT02576717) of ozanimod 0.92 mg/d. This analysis (January 2020‒October 2021 [serology] and January 2022 [clinical outcomes]) included DAYBREAK participants who received SARS-CoV-2 vaccines (fully vaccinated) and/or had COVID-19 adverse events. Receptor binding domain (RBD) antibody levels and nucleocapsid antibody positivity were analyzed using Roche Elecsys assays. Log2 RBD antibody levels were compared between groups using t-tests.

Results:

Among the 148 vaccinated participants with serological data, 39 participants had serologically confirmed SARS-CoV-2 exposure. After full vaccination, RBD seroconversion occurred in 100% (n=39/39) of nucleocapsid antibody positive and most (n=98/109) nucleocapsid antibody negative participants (with 100% seroconversion in nucleocapsid antibody negative participants receiving mRNA vaccines [n=80/80]). Significantly higher RBD antibody levels were observed in the vaccinated nucleocapsid antibody positive vs negative vaccinated participants (median [range], U/mL: 2259 [12.4–44260.0] vs 138 [0.4–4572.0], respectively, P<0.0001). COVID-19 adverse events were reported in 15/148 participants, all nonserious events (confirmed=12, suspected=3). Ozanimod treatment was continued in 9 participants and interrupted in 5 (1 unknown). Eleven participants recovered by the time of data cut off, and one recovered with sequelae (cough and loss of sense of smell).

Conclusions:

Participants with RMS receiving ozanimod mount a serologic response to SARS-CoV-2 infection and vaccination. COVID-19 events in these fully vaccinated participants were nonserious. A limitation of this research is its retrospective nature and the potential for selection bias towards higher-risk individuals.