RT Journal Article
SR Electronic
T1 Vaccine escape, increased breakthrough and reinfection in infliximab-treated patients with IBD during the Omicron wave of the SARS-CoV-2 pandemic
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 295
OP 305
DO 10.1136/gutjnl-2022-327570
VO 72
IS 2
A1 Nicholas A Kennedy
A1 Malik Janjua
A1 Neil Chanchlani
A1 Simeng Lin
A1 Claire Bewshea
A1 Rachel Nice
A1 Timothy J McDonald
A1 Cressida Auckland
A1 Lorna W Harries
A1 Merlin Davies
A1 Stephen Michell
A1 Klaartje B Kok
A1 Christopher A Lamb
A1 Philip J Smith
A1 Ailsa L Hart
A1 Richard CG Pollok
A1 Charlie W Lees
A1 Rosemary J Boyton
A1 Daniel M Altmann
A1 Shaji Sebastian
A1 Nicholas Powell
A1 James R Goodhand
A1 Tariq Ahmad
YR 2023
UL http://gut.bmj.com/content/72/2/295.abstract
AB 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 was 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.Data are available on reasonable request. The study protocol including the statistical analysis plan is available at www.clarityibd.org. Individual participant de-identified data that underlie the results reported in this article will be available immediately after publication for a period of 5 years. The data will be made available to investigators whose proposed use of the data has been approved by an independent review committee. Analyses will be restricted to the aims in the approved proposal. Proposals should be directed to tariq.ahmad1@nhs.net; to gain access data requestors will need to sign a data access agreement.