ABSTRACT
Background: 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. Method(s): 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. Result(s): Demographics were similar between the mRNA and nonmRNA 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. Conclusion(s): 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.
ABSTRACT
Introduction: Multiple sclerosis disease-modifying therapies, including sphingosine 1-phosphate receptor modulators, may attenuate the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. Objective(s): To describe the serological response and clinical outcomes of SARS-CoV-2 infection and vaccination in ozanimodtreated participants with relapsing multiple sclerosis (RMS) in an open-label extension (OLE) trial. Method(s): 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 SARSCoV-2 vaccines (fully vaccinated) and/or had COVID-19 adverse events. Receptor binding domain (RBD) antibody levels and nucleocapsid antibody positivity were analysed using Roche Elecsys assays. Log2 RBD antibody levels were compared between groups using t-tests. Result(s): 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). Conclusion(s): 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.