Kennedy, NA;
Janjua, M;
Chanchlani, N;
Lin, S;
Bewshea, C;
Nice, R;
McDonald, TJ;
Auckland, C;
Harries, LW;
Davies, M;
et al.
Kennedy, NA; Janjua, M; Chanchlani, N; Lin, S; Bewshea, C; Nice, R; McDonald, TJ; Auckland, C; Harries, LW; Davies, M; Michell, S; Kok, KB; Lamb, CA; Smith, PJ; Hart, AL; Pollok, RC; Lees, CW; Boyton, RJ; Altmann, DM; Sebastian, S; Powell, N; Goodhand, JR; Ahmad, T
(2022)
Vaccine escape, increased breakthrough and reinfection in infliximab-treated patients with IBD during the Omicron wave of the SARS-CoV-2 pandemic.
Gut, 72 (2).
pp. 295-305.
ISSN 1468-3288
https://doi.org/10.1136/gutjnl-2022-327570
SGUL Authors: Pollok, Richard Charles G
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Abstract
OBJECTIVE: Antitumour necrosis factor (TNF) drugs impair serological responses following SARS-CoV-2 vaccination. We sought to assess if a third dose of a messenger RNA (mRNA)-based vaccine substantially boosted anti-SARS-CoV-2 antibody responses and protective immunity in infliximab-treated patients with IBD. DESIGN: Third dose vaccine induced anti-SARS-CoV-2 spike (anti-S) receptor-binding domain (RBD) antibody responses, breakthrough SARS-CoV-2 infection, reinfection and persistent oropharyngeal carriage in patients with IBD treated with infliximab were compared with a reference cohort treated with vedolizumab from the impaCt of bioLogic therApy on saRs-cov-2 Infection and immuniTY (CLARITY) IBD study. RESULTS: Geometric mean (SD) anti-S RBD antibody concentrations increased in both groups following a third dose of an mRNA-based vaccine. However, concentrations were lower in patients treated with infliximab than vedolizumab, irrespective of whether their first two primary vaccine doses were ChAdOx1 nCoV-19 (1856 U/mL (5.2) vs 10 728 U/mL (3.1), p<0.0001) or BNT162b2 vaccines (2164 U/mL (4.1) vs 15 116 U/mL (3.4), p<0.0001). However, no differences in anti-S RBD antibody concentrations were seen following third and fourth doses of an mRNA-based vaccine, irrespective of the combination of primary vaccinations received. Post-third dose, anti-S RBD antibody half-life estimates were shorter in infliximab-treated than vedolizumab-treated patients (37.0 days (95% CI 35.6 to 38.6) vs 52.0 days (95% CI 49.0 to 55.4), p<0.0001).Compared with vedolizumab-treated, infliximab-treated patients were more likely to experience SARS-CoV-2 breakthrough infection (HR 2.23 (95% CI 1.46 to 3.38), p=0.00018) and reinfection (HR 2.10 (95% CI 1.31 to 3.35), p=0.0019), but this effect was uncoupled from third vaccine dose anti-S RBD antibody concentrations. Reinfection occurred predominantly during the Omicron wave and were predicted by SARS-CoV-2 antinucleocapsid concentrations after the initial infection. We did not observe persistent oropharyngeal carriage of SARS-CoV-2. Hospitalisations and deaths were uncommon in both groups. CONCLUSIONS: Following a third dose of an mRNA-based vaccine, infliximab was associated with attenuated serological responses and more SARS-CoV-2 breakthrough infection and reinfection which were not predicted by the magnitude of anti-S RBD responses, indicative of vaccine escape by the Omicron variant. TRIAL REGISTRATION NUMBER: ISRCTN45176516.
Item Type: | Article | ||||||||||||||||||||||||||||||||||||||||||
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Additional Information: | This article has been accepted for publication in Gut, 2022 following peer review, and the Version of Record can be accessed online at http://doi.org/10.1136/gutjnl-2022-327570. © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ. | ||||||||||||||||||||||||||||||||||||||||||
Keywords: | COVID-19, biological, immunosuppression, inflammatory bowel disease, infliximab, vaccination, vedolizumab, 1103 Clinical Sciences, 1114 Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology | ||||||||||||||||||||||||||||||||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Infection and Immunity Research Institute (INII) | ||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Gut | ||||||||||||||||||||||||||||||||||||||||||
ISSN: | 1468-3288 | ||||||||||||||||||||||||||||||||||||||||||
Language: | eng | ||||||||||||||||||||||||||||||||||||||||||
Publisher License: | Creative Commons: Attribution-Noncommercial 4.0 | ||||||||||||||||||||||||||||||||||||||||||
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PubMed ID: | 35902214 | ||||||||||||||||||||||||||||||||||||||||||
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URI: | https://openaccess.sgul.ac.uk/id/eprint/114625 | ||||||||||||||||||||||||||||||||||||||||||
Publisher's version: | https://doi.org/10.1136/gutjnl-2022-327570 |
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