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    OP22 Antibody decay, T cell immunity and breakthrough infections following SARS-CoV-2 vaccination in infliximab- and vedolizumab-treated patients

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    URI
    https://rde.dspace-express.com/handle/11287/622389
    Author
    Lin, S
    Kennedy, N A
    Saifuddin, A
    Muñoz Sandoval, D
    Reynolds, C J
    Seoane, R C
    Kottoor, S H
    Pieper, F P
    Lin, K M
    Butler, D K
    Chanchlani, N
    Nice, R
    Chee, D
    Bewshea, C
    Janjua, M
    McDonald, T J
    Sebastian, S
    Alexander, J L
    Constable, L
    Lee, J C
    Murray, C D
    Hart, A L
    Irving, P M
    Jones, G R
    Kok, K B
    Lamb, C A
    Lees, C W
    Altmann, D M
    Boyton, R J
    Goodhand, J R
    Powell, N
    Ahmad, T.
    IBD, CLARITY
    Journal
    Journal of Crohn's and Colitis
    Type
    Journal Article
    Publisher
    Oxford University Press
    DOI
    10.1093/ecco-jcc/jjab232.021
    Rights
    Copyright © 2022, Oxford University Press
    Metadata
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    Abstract
    Antibody responses following SARS-CoV-2 infection or a single-dose of SARS-CoV-2 vaccine are impaired in patients with inflammatory bowel disease treated with anti-TNF compared to those treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody.Here we sought to determine if patients treated with infliximab have attenuated serological and T cell responses and an increased risk of breakthrough COVID-19 infection following primary SARS-CoV-2 vaccination.Anti-spike (S) receptor binding domain (RBD) antibody concentration in 2306 infliximab-treated patients were compared to a cohort of 1045 vedolizumab-treated patients. Our primary outcome was anti-S RBD antibodies 2 to 10 weeks after a second dose of the BNT162b2 or ChAdOx1 nCoV-19 vaccines. Secondary outcomes were anti-spike T cell responses, durability of vaccine responses and risk of breakthrough infections following two doses of vaccine.Anti-S RBD antibody concentrations were lower in patients treated with infliximab than in those treated with vedolizumab, following a second dose of BNT162b2 (567.3 U/mL [6.1] vs 4601.1 U/mL [5.3], p <0.0001) and ChAdOx1 nCoV-19 (183.9 U/mL [5.0] vs 789.4 U/mL [3.5], p <0.0001) vaccines (Fig. 1). Vaccination with the BNT162b2 vaccine compared to the ChAdOx1 nCoV-19 was independently associated with a 3.7-fold [95% CI 3.30 – 4.13] higher anti-S RBD antibody concentration (p < 0.0001) (Fig. 2).There were no significant differences in the magnitude of anti-spike T cell responses observed in infliximab- compared with vedolizumab-treated patients after one or two doses of either vaccine.Antibody half-life was shorter in infliximab- than vedolizumab-treated patients following two-doses of BNT162b2 (4.0 weeks [95% CI 3.8 – 4.1] vs 7.2 weeks [95% CI 6.8 – 7.6]) and ChAdOx1 nCoV-19 (5.3 weeks [95% CI 5.1 – 5.5] vs 9.3 weeks [95% CI 8.5 – 10.2], p value < 0.0001).Breakthrough SARS-CoV-2 infections were more frequent (5.8% (202/3467) vs 3.9% (66/1691), p = 0.0032) and the time to breakthrough shorter in patients treated with infliximab than vedolizumab (p = 0.0023) (Fig. 3).Higher anti-S RBD antibody concentrations following a second dose of SARS-CoV-2 vaccine protected against breakthrough SARS-CoV-2 infection: overall, for every 10-fold rise in anti-S RBD antibody level we observed a 0.8-fold reduction in odds of breakthrough infection ([95% CI 0.70 – 0.99], p = 0.035). Infliximab was associated with attenuated, less durable vaccine induced anti-S RBD antibody responses and a 50% increase in breakthrough SARS-CoV-2 infection. Further follow-up is required to assess whether third primary doses can mitigate the effects of infliximab on anti-S RBD antibody responses.
    Publisher URL
    https://academic.oup.com/ecco-jcc/article/16/Supplement_1/i023/6512460
    Note
    The article is available via Open Access. Click on the 'Additional link' above to access the full-text.
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    • 2022 Eastern publications
    • COVID-19
    • Gastroenterology

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