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Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study
Version 1
: Received: 27 August 2024 / Approved: 28 August 2024 / Online: 28 August 2024 (10:39:29 CEST)
How to cite:
Hitchon, C. A.; Bowdish, D. M. E.; Boire, G.; Fortin, P. R.; Flamand, L.; Chandran, V.; Dayam, R. M.; Gingras, A.-C.; Card, C. M.; Colmegna, I.; Larché, M. J.; Kaplan, G. G.; Lukusa, L.; Lee, J. L.; Bernatsky, S. Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study. Preprints2024, 2024081998. https://doi.org/10.20944/preprints202408.1998.v1
Hitchon, C. A.; Bowdish, D. M. E.; Boire, G.; Fortin, P. R.; Flamand, L.; Chandran, V.; Dayam, R. M.; Gingras, A.-C.; Card, C. M.; Colmegna, I.; Larché, M. J.; Kaplan, G. G.; Lukusa, L.; Lee, J. L.; Bernatsky, S. Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study. Preprints 2024, 2024081998. https://doi.org/10.20944/preprints202408.1998.v1
Hitchon, C. A.; Bowdish, D. M. E.; Boire, G.; Fortin, P. R.; Flamand, L.; Chandran, V.; Dayam, R. M.; Gingras, A.-C.; Card, C. M.; Colmegna, I.; Larché, M. J.; Kaplan, G. G.; Lukusa, L.; Lee, J. L.; Bernatsky, S. Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study. Preprints2024, 2024081998. https://doi.org/10.20944/preprints202408.1998.v1
APA Style
Hitchon, C. A., Bowdish, D. M. E., Boire, G., Fortin, P. R., Flamand, L., Chandran, V., Dayam, R. M., Gingras, A. C., Card, C. M., Colmegna, I., Larché, M. J., Kaplan, G. G., Lukusa, L., Lee, J. L., & Bernatsky, S. (2024). Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study. Preprints. https://doi.org/10.20944/preprints202408.1998.v1
Chicago/Turabian Style
Hitchon, C. A., Jennifer LF Lee and Sasha Bernatsky. 2024 "Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study" Preprints. https://doi.org/10.20944/preprints202408.1998.v1
Abstract
Objective: SARS-CoV-2 remains the third most common cause of death in North America. We studied methotrexate and tumor necrosis factor inhibitor (TNFi) effects on neutralization responses post-COVID vaccination, in immune-mediated inflammatory disease(IMID).
Methods: Prospective data and sera on adults with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA) and systemic lupus (SLE) were collected at 6 academic centres in Alberta, Manitoba, Ontario, and Quebec between 2022-2023. Sera from two time points were evaluated for each subject. Neutralization studies were divided between 5 laboratories, and each lab’s results analyzed separately using multivariate generalized logit models (ordinal outcomes: absent, low, medium, and high neutralization). Odds ratios (ORs) for methotrexate and TNFi effects were adjusted for demographics, IMID, other biologics and immunosuppressives, prednisone, COVID vaccinations (number/type), and infections in the 6 months prior to sample. Adjusted ORs for methotrexate and TNFi were then pooled in random-effects meta-analyses (separately for ancestral, and Omicron BA1 and BA5 strains).
Results: Of 479 individuals (958 samples), 292 (61%) were IBD, 141 (29.4%) RA, and the remainder PsA, SpA and SLE. Mean age was 57 (62.2 % female). For both individual labs and the meta-analyses, 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.
Public Health and Healthcare, Public Health and Health Services
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