Vaccine escape, increased breakthrough and reinfection in infliximab-treated patients with IBD during the Omicron wave of the SARS-CoV-2 pandemic

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.

Author list

Affiliations:

  1. Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
  2. Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK
  3. Department of Biochemistry, Exeter Clinical Laboratory International, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
  4. Department of Microbiology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
  5. Institute of Biomedical and Clinical Sciences, University of Exeter, Exeter, UK
  6. College of Life and Environmental Sciences, University of Exeter, Exeter, UK
  7. Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK
  8. Department of Gastroenterology, Royal London Hospital, Barts Health NHS Trust, The Royal London Hospital, London, UK
  9. Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  10. Translational & Clinical Research Institute, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK
  11. Department of Gastroenterology, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
  12. Department of Gastroenterology, St Mark’s Hospital and Academic Institute, London, UK
  13. Department of Gastroenterology, St George’s University Hospitals NHS Foundation Trust, London, UK
  14. Institute for Infection & Immunity, St George’s University of London, London, UK
  15. Department of Gastroenterology, Western General Hospital, Edinburgh, UK
  16. Institute of Genetic and Molecular Medicine, University of Edinburgh Western General Hospital, Edinburgh, UK
  17. Department of Infectious Disease, Imperial College London, London, UK
  18. Lung Division, Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
  19. Department of Immunology and Inflammation, Imperial College London, London, UK
  20. IBD Unit, Department of Gastroenterology, Hull University Teaching Hospitals NHS Trust, Hull, UK

Authors:

Nicholas A Kennedy1,2 Malik Janjua1,2 Neil Chanchlani1,2 Simeng Lin1,2 Claire Bewshea2 Rachel Nice2,3 Timothy J McDonald3 Cressida Auckland4 Lorna W Harries5 Merlin Davies5 Stephen Michell6 Klaartje B Kok7,8 Christopher A Lamb 9,10 Philip J Smith11Ailsa L Hart12 Richard CG Pollok13,14 Charlie W Lees15,16 Rosemary J Boyton17,18 Daniel M Altmann Shaji Sebastian20,21 Nicholas Powell22,23 James R Goodhand19 Tariq Ahmad1,2  

Novel Coronavirus SARS-CoV-2

10.1136/gutjnl-2022-327570

BMJ - Gut

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