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

Carol Hitchon¹, Dawn Bowdish², Gilles Boire³, Paul Fortin⁴, Louis Flamand⁵, Vinod Chandran⁶, Roya M Dayam⁷, Anne-Claude Gingras⁸, Catherine Card⁹, Ines Colmegna¹⁰, Maggie Larche², Gil Kaplan¹¹, Luck Lukusa¹², Jennifer Lee¹² and Sasha Bernatsky¹³, and SUCCEED investigative team, ¹University of Manitoba, Winnipeg, MB, Canada, ²McMaster University, Hamilton, ON, Canada, ³Retired, Sherbrooke, QC, Canada, ⁴Centre ARThrite - CHU de Québec - Université Laval, Quebec, QC, Canada, ⁵Centre Hospitalier Universitaire (CHU) de Québec-Université Laval Research Center, Quebec City, ⁶University of Toronto, Toronto, ON, Canada, ⁷Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada, ⁸Lunenfeld-Tanenbaum Research Institute, Toronto, ON, Canada, ⁹National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada, ¹⁰The Research Institute of the McGill University Health Centre, Montréal, QC, Canada, ¹¹University of Calgary, Calgary, AB, Canada, ¹²The Research Institute of the McGill University Health Centre, Montreal, QC, Canada, ¹³Research Institute of the McGill University Health Centre, Montreal, QC, Canada

Meeting: ACR Convergence 2024

Keywords: Anti-TNF Drugs, COVID-19, Disease-Modifying Antirheumatic Drugs (Dmards), Miscellaneous Rheumatic and Inflammatory Diseases, rheumatoid arthritis

Session Information

Date: Saturday, November 16, 2024

Title: Epidemiology & Public Health Poster I

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: Given ongoing SARS-CoV-2 circulation, COVID-19 vaccination response in immune-mediated inflammatory disease (IMID) remains a key issue, particularly regarding effects of common immunosuppressives like methotrexate and tumor necrosis factor inhibitors (TNFi). To date, studies focussed on a single disease and/or a single centre, or assessed only ancestral strains and/or only the presence of antibodies and not viral neutralization ability. When combining data across centres to achieve a larger and diverse sample, sophisticated modeling must allow for differences across centres, while aiming to achieve a single estimate of effects. Our purpose was to overcome these challenges.

Methods: Prospectively collected data and sera on adults with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE) were collected at academic centres in Alberta, Manitoba, Ontario, and Quebec. Five labs were used, all performed neutralization for the ancestral strain, four labs also assessed omicron BA1, and three assessed ancestral BA5. Two serum samples from each participant, collected between 2022-2023, were assessed. Each lab’s results were analyzed separately using multivariate generalized logit models (with ordinal outcomes for no, low, medium, and high neutralization ability) and then pooled in random-effects meta-analyses for ancestral, BA1 and BA5 strains.

Results: We studied 479 individuals; 292 (61%) were IBD, 141 (29.4%) RA, 24 PsA (5%), 13 SpA (2.7%) and 9 SLE (1.9%). Most (n=447, 93.3%) individuals were white, 62.2 % were female, and the mean age was 56.8 (standard deviation 14.8) years. Other characteristics are shown in Table 1. Table 2 shows the ORs, adjusted for sex, age, race/ethnicity, IMID, DMARD, biologics, prednisone, and details of past COVID vaccinations and infections. For both individual labs and the meta-analyses, adjusted ORs suggested that TNFi and methotrexate were independently associated with less neutralization ability.

Conclusion: Neutralization responses in immunosuppressed IMID hosts may be diminished by both TNFi and methotrexate in an independent manner.

Table 1: Description of SUCCEED participants

Table 2. Multivariate ordered logit regressiona and random-effects meta-analysesb: Adjusted odds ratios (aOR) for methotrexate and tumor-necrosis factor inhibitors (TNFi) effects.

Disclosures: C. Hitchon: None; D. Bowdish: AstraZeneca, 1, Federal Government, 6, Pfizer, 1; G. Boire: AbbVie/Abbott, 1, Biocon, 5, Orimed, 2, 6, Otsuka, 1, Pfizer, 5, Sanofi, 1; P. Fortin: AstraZeneca, 2, 6, GlaxoSmithKlein(GSK), 2, 6, Moderna, 2; L. Flamand: None; V. Chandran: AbbVie/Abbott, 1, 5, AstraZeneca, 12, Spousal employment, Bristol-Myers Squibb(BMS), 1, Eli Lilly, 1, Janssen, 1, Novartis, 1, UCB, 1; R. Dayam: None; A. Gingras: None; C. Card: None; I. Colmegna: None; M. Larche: None; G. Kaplan: AbbVie/Abbott, 6, Ferring, 5, Janssen, 6, Pfizer, 6, Takeda, 2, 6; L. Lukusa: None; J. Lee: None; S. Bernatsky: None.

To cite this abstract in AMA style:

Hitchon C, Bowdish D, Boire G, Fortin P, Flamand L, Chandran V, Dayam R, Gingras A, Card C, Colmegna I, Larche M, Kaplan G, Lukusa L, Lee J, Bernatsky S. Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies After SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/methotrexate-and-tumor-necrosis-factor-inhibitors-independently-decrease-neutralizing-antibodies-after-sars-cov-2-vaccination-updated-results-from-the-succeed-study/. Accessed .

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/methotrexate-and-tumor-necrosis-factor-inhibitors-independently-decrease-neutralizing-antibodies-after-sars-cov-2-vaccination-updated-results-from-the-succeed-study/