P516 Humoral immune responses to SARS-CoV-2 vaccines in an ozanimod open-label extension study

Caldera, F.(1)*;Maddux, R.(2);Ungaro, R.(3);Kaur, A.(2);Brown, E.(2);Hu, S.(2);Sheffield, J.K.(2);Silva, D.(2);Harris, S.(2);Cree, B.A.C.(4);

(1)University of Wisconsin School of Medicine and Public Health, Gastroenterology and Hepatology, Madison, United States;(2)Bristol Myers Squibb, Clinical Research, Princeton, United States;(3)Icahn School of Medicine at Mount Sinai, Gastroenterology, New York, United States;(4)University of California San Francisco, Weill Institute for Neurosciences- Department of Neurology, San Francisco, United States;


Ozanimod, an oral sphingosine 1-phosphate receptor modulator, is approved in the European Union and United States for the treatment of moderately to severely active ulcerative colitis (UC) and relapsing multiple sclerosis (RMS). A previous analysis of data from UC and multiple sclerosis (MS) open-label extension (OLE) studies showed that most patients with confirmed coronavirus infection (COVID-19) had nonserious infections, recovered, and did not require ozanimod discontinuation. Some immunomodulators and biologics may attenuate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response; therefore, this analysis evaluated humoral immune responses and predictors of response to SARS-CoV-2 vaccination in patients with RMS treated with ozanimod.


RMS participants 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) included DAYBREAK participants receiving mRNA or non-mRNA SARS-CoV-2 vaccines (1–2 doses, vaccine-dependent) with no evidence of recent infection (ie, nucleocapsid antibody negative). Receptor binding domain (RBD) antibody titers were analysed (Elecsys Anti-SARS-CoV-2 assay; Roche Diagnostics, Basel, Switzerland) prevaccination, after 1 dose, and <4, 4–8, 8–12, and >12 weeks after full vaccination. Fisher’s exact tests and regression models determined association with seroconversion and log2 antibody levels.


Demographics were similar between the mRNA and non-mRNA vaccine recipients (Table). Seroconversion (≥0.8 U/mL spike RBD antibody) occurred in 100% (80/80) of fully vaccinated mRNA recipients and 62% (18/29) of fully vaccinated non-mRNA vaccine recipients. Higher spike RBD antibody levels were seen with mRNA (grand mean: 512.6 U/mL, range: 1.3–4572.0) vs non-mRNA (grand mean: 39.3 U/mL, range: 0.4–368.5) vaccines at all time points studied. Vaccination with a non-mRNA vaccine predicted lower antibody levels (beta: –5.90 [95% CI: –6.99 to –4.82]; P<0.0001) and less seroconversion (Fisher’s exact: P<0.0001), whereas age, sex, body mass index, and absolute lymphocyte count (ALC) did not.


Participants receiving ozanimod developed humoral immune response to SARS-CoV-2 vaccines, with 100% seroconversion after mRNA vaccination; this was independent of demographic characteristics and ALC levels at time of vaccination. However, some participants developed lower antibody concentrations and may benefit from booster doses. These findings provide important information for physicians managing ozanimod-treated patients with UC or MS.