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

<b>Objective:</b> 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). <b>Me...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2024-09-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/12/9/1061
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author 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
author_facet 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
author_sort Carol A Hitchon
collection DOAJ
description <b>Objective:</b> 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). <b>Methods:</b> 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). <b>Results:</b> 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. <b>Conclusions:</b> 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.
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spelling doaj-art-8d13f31f9a0b43d4b59453a2c5cf209b2025-08-20T01:55:57ZengMDPI AGVaccines2076-393X2024-09-01129106110.3390/vaccines12091061Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED StudyCarol A Hitchon0Dawn M. E. Bowdish1Gilles Boire2Paul R. Fortin3Louis Flamand4Vinod Chandran5Roya M. Dayam6Anne-Claude Gingras7Catherine M. Card8Inés Colmegna9Maggie J. Larché10Gilaad G. Kaplan11Luck Lukusa12Jennifer L.F. Lee13Sasha Bernatsky14on behalf of the SUCCEED Investigative TeamDepartment of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, CanadaMcMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4L8, CanadaDivision of Rheumatology, Department of Medicine, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaCentre de Recherche ARThrite—UL, Division of Rheumatology, Department of Medicine, CHU de Québec, Université Laval, Québec City, QC G1V 4G2, CanadaAxe Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec, Université Laval, Québec City, QC G1V 4G2, CanadaSchroeder Arthritis Institute and Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, CanadaLunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, CanadaLunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, CanadaDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3T 2N2, CanadaDepartment of Medicine, McGill University, Montreal, QC H3A 0E9, CanadaDivision of Rheumatology, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, CanadaDivision of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB T2N 1N4, CanadaThe Research Institute of the McGill University Health Centre, McGill University, Montreal, QC H3A 0E9, CanadaThe Research Institute of the McGill University Health Centre, McGill University, Montreal, QC H3A 0E9, CanadaDepartment of Medicine, McGill University, Montreal, QC H3A 0E9, Canada<b>Objective:</b> 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). <b>Methods:</b> 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). <b>Results:</b> 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. <b>Conclusions:</b> 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.https://www.mdpi.com/2076-393X/12/9/1061COVID-19vaccinationimmune-mediated inflammatory diseasemethotrexatetumor necrosis factor inhibitorsautoimmune diseases
spellingShingle 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
Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study
Vaccines
COVID-19
vaccination
immune-mediated inflammatory disease
methotrexate
tumor necrosis factor inhibitors
autoimmune diseases
title Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study
title_full Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study
title_fullStr Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study
title_full_unstemmed Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study
title_short Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study
title_sort methotrexate and tumor necrosis factor inhibitors independently decrease neutralizing antibodies after sars cov 2 vaccination updated results from the succeed study
topic COVID-19
vaccination
immune-mediated inflammatory disease
methotrexate
tumor necrosis factor inhibitors
autoimmune diseases
url https://www.mdpi.com/2076-393X/12/9/1061
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