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
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.
