Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study

Carol A Hitchon; Dawn M. E. Bowdish; Gilles Boire; Paul R. Fortin; Louis Flamand; Vinod Chandran; Roya M. Dayam; Anne-Claude Gingras; Catherine M. Card; Inés Colmegna; Maggie J. Larché; Gilaad G. Kaplan; Luck Lukusa; Jennifer L.F. Lee; Sasha Bernatsky; on behalf of the SUCCEED Investigative Team

doi:10.3390/vaccines12091061

Vaccines (Sep 2024)

Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study

Carol A Hitchon,
Dawn M. E. Bowdish,
Gilles Boire,
Paul R. Fortin,
Louis Flamand,
Vinod Chandran,
Roya M. Dayam,
Anne-Claude Gingras,
Catherine M. Card,
Inés Colmegna,
Maggie J. Larché,
Gilaad G. Kaplan,
Luck Lukusa,
Jennifer L.F. Lee,
Sasha Bernatsky,
on behalf of the SUCCEED Investigative Team

Affiliations

Carol A Hitchon: Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
Dawn M. E. Bowdish: McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4L8, Canada
Gilles Boire: Division of Rheumatology, Department of Medicine, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
Paul R. Fortin: Centre de Recherche ARThrite—UL, Division of Rheumatology, Department of Medicine, CHU de Québec, Université Laval, Québec City, QC G1V 4G2, Canada
Louis Flamand: Axe Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec, Université Laval, Québec City, QC G1V 4G2, Canada
Vinod Chandran: Schroeder Arthritis Institute and Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada
Roya M. Dayam: Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
Anne-Claude Gingras: Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
Catherine M. Card: Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
Inés Colmegna: Department of Medicine, McGill University, Montreal, QC H3A 0E9, Canada
Maggie J. Larché: Division of Rheumatology, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada
Gilaad G. Kaplan: Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada
Luck Lukusa: The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC H3A 0E9, Canada
Jennifer L.F. Lee: The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC H3A 0E9, Canada
Sasha Bernatsky: Department of Medicine, McGill University, Montreal, QC H3A 0E9, Canada
on behalf of the SUCCEED Investigative Team

DOI: https://doi.org/10.3390/vaccines12091061
Journal volume & issue: Vol. 12, no. 9
p. 1061

Abstract

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Objective: SARS-CoV-2 remains the third most common cause of death in North America. We studied the effects of methotrexate and tumor necrosis factor inhibitor (TNFi) on neutralization responses after COVID-19 vaccination in immune-mediated inflammatory disease (IMID). Methods: Prospective data and sera of adults with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and systemic lupus (SLE) were collected at six academic centers in Alberta, Manitoba, Ontario, and Quebec between 2022 and 2023. Sera from two time points were evaluated for each subject. Neutralization studies were divided between five laboratories, and each lab’s results were analyzed separately using multivariate generalized logit models (ordinal outcomes: absent, low, medium, and high neutralization). Odds ratios (ORs) for the effects of methotrexate and TNFi were adjusted for demographics, IMID, other biologics and immunosuppressives, prednisone, COVID-19 vaccinations (number/type), and infections in the 6 months prior to sampling. The adjusted ORs for methotrexate and TNFi were then pooled in random-effects meta-analyses (separately for the ancestral strains and the Omicron BA1 and BA5 strains). Results: Of 479 individuals (958 samples), 292 (61%) were IBD, 141 (29.4%) were RA, and the remainder were PsA, SpA, and SLE. The mean age was 57 (62.2% female). For both the individual labs and the meta-analyses, the adjusted ORs suggested independent negative effects of TNFi and methotrexate on neutralization. The meta-analysis adjusted ORs for TNFi were 0.56 (95% confidence interval (CI) 0.39, 0.81) for the ancestral strain and 0.56 (95% CI 0.39, 0.81) for BA5. The meta-analysis adjusted OR for methotrexate was 0.39 (95% CI 0.19, 0.76) for BA1. Conclusions: SARS-CoV-2 neutralization in vaccinated IMID was diminished independently by TNFi and methotrexate. As SARS-CoV-2 circulation continues, ongoing vigilance regarding optimized vaccination is required.

Published in Vaccines

ISSN: 2076-393X (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine
Website: http://www.mdpi.com/journal/vaccines

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