E0367 - Humoral Immune Responses to SARS-CoV-2 Vaccines in an Ozanimod Open-Label Extension Study

Tuesday, October 25, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Freddy Caldera, DO, MS

University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin

Freddy Caldera, DO, MS¹, Rachel Maddux, PhD², Ryan Ungaro, MD, MS³, Amandeep Kaur, MSc², Elizabeth Brown, PhD², Sarah Hu, PhD², James K. Sheffield, MD, MBA, MS², Diego Silva, MD, PhD², Sarah Harris, PhD², Bruce AC. Cree, MD, PhD⁴
¹University of Wisconsin School of Medicine and Public Health, Madison, WI; ²Bristol Myers Squibb, Princeton, NJ; ³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴University of California San Francisco, San Francisco, CA

Introduction: Ozanimod (OZA), an oral S1P receptor modulator, is approved in the US and EU 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 (pts) with confirmed coronavirus infection (COVID-19) had nonserious infections, recovered, and did not require OZA discontinuation. As some immunomodulators and biologics may attenuate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response, this analysis evaluated humoral immune responses and predictors of response to SARS-CoV-2 vaccination in pts with RMS treated with OZA.

Methods: RMS participants who completed a phase 1-3 OZA trial could enter an OLE trial (DAYBREAK; NCT02576717) of OZA 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 analyzed (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.

Results: 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 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) 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.

Discussion: Participants receiving OZA 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 OZA-treated pts with UC or MS.

Table. Demographics and clinical characteristics of fully vaccinated participants
Characteristics	mRNA vaccine recipients (n=80)	Non-mRNA vaccine recipients (n=29)
White, n (%)	78 (97.5)	29 (100.0)
Non-Hispanic, n (%)	76 (95.0)	28 (96.6)
Eastern European, n (%)	41 (51.3)	22 (75.9)
Age, years, mean (range)	40.4 (23-56)	41.6 (28-56)
BMI, kg/m², mean (range)	24.6 (16.8-42.0)	25 (17.3-33.8)
Female, %	74%	72%
Days on OZA, mean, days (range)	1676.9 (1398-1967)	1620.5 (1448-1869)
BMI, body mass index; CI, confidence interval.

Disclosures:

Freddy Caldera: Arena – Consultant. Celgene – Consultant. GlaxoSmithKline – Consultant. Sanofi – Grant/Research Support. Takeda – Consultant, Grant/Research Support.

Rachel Maddux: Bristol Myers Squibb – Employee.

Ryan Ungaro: AbbVie – Grant/Research Support. Boehringer Ingelheim – Grant/Research Support. Eli Lilly – Consultant. Janssen – Consultant. Pfizer – Consultant, Grant/Research Support. Takeda – Consultant.

Amandeep Kaur: Bristol Myers Squibb – Employee, Stock-publicly held company(excluding mutual/index funds).

Elizabeth Brown: Bristol Myers Squibb – Employee, Stock-publicly held company(excluding mutual/index funds).

Sarah Hu: Bristol Myers Squibb – Employee, Stock-publicly held company(excluding mutual/index funds).

James Sheffield: Bristol Myers Squibb – Employee, Stock-publicly held company(excluding mutual/index funds).

Diego Silva: Bristol Myers Squibb – Employee, Stock-publicly held company(excluding mutual/index funds).

Sarah Harris: Bristol Myers Squibb – Employee, Stock-publicly held company(excluding mutual/index funds).

Bruce Cree: Alexion – Consultant. Atara – Consultant. Autobahn – Consultant. Avotres – Consultant. Biogen – Consultant. EMD Serono – Consultant. Genentech – Grant/Research Support. Gossamer Bio – Consultant. Horizon – Consultant. Neuron23 – Consultant. Novartis – Consultant. Sanofi – Consultant. TG Therapeutics – Consultant. Therini Bio – Consultant.

Freddy Caldera, DO, MS¹, Rachel Maddux, PhD², Ryan Ungaro, MD, MS³, Amandeep Kaur, MSc², Elizabeth Brown, PhD², Sarah Hu, PhD², James K. Sheffield, MD, MBA, MS², Diego Silva, MD, PhD², Sarah Harris, PhD², Bruce AC. Cree, MD, PhD⁴. E0367 - Humoral Immune Responses to SARS-CoV-2 Vaccines in an Ozanimod Open-Label Extension Study, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.