Abstract

Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD

Gut. 2021 Apr 26;gutjnl-2021-324789.doi: 10.1136/gutjnl-2021-324789. Online ahead of print.

Nicholas A Kennedy # 1 2, Simeng Lin # 1 2, James R Goodhand # 1 2, Neil Chanchlani 1 2, Benjamin Hamilton 1 2, Claire Bewshea 2, Rachel Nice 2 3, Desmond Chee 1 2, Jr Fraser Cummings 4, Aileen Fraser 5, Peter M Irving 6 7, Nikolaos Kamperidis 8, Klaartje B Kok 9 10, Christopher Andrew Lamb 11 12, Jonathan Macdonald 13 14, Shameer Mehta 15, Richard Cg Pollok 16 17, Tim Raine 18, Philip J Smith 19, Ajay Mark Verma 20, Simon Jochum 21, Timothy J McDonald 3, Shaji Sebastian 22 23, Charlie W Lees 24 25, Nick Powell # 26 27, Tariq Ahmad # 28 2, Contributors to the CLARITY IBD study

 
     

Author information

  • 1Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • 2Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • 3Biochemistry, Exeter Clinical Laboratory International, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • 4Gastroenterology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
  • 5Gastroenterology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.
  • 6Gastroenterology, Guy's and St Thomas' Hospitals NHS Trust, London, UK.
  • 7School of Immunology & Microbial Sciences, King's College London, London, UK.
  • 8Gastroenterology, St Marks Hospital and Academic Institute, London, UK, London, UK.
  • 9Gastroenterology, Barts and The London NHS Trust, London, UK.
  • 10Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry Blizard Institute, London, UK.
  • 11Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
  • 12Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • 13Gastroenterology, Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK.
  • 14School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK.
  • 15Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK.
  • 16Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK.
  • 17Institute for Infection & Immunity, University of London St George's, London, UK.
  • 18Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  • 19Gastroenterology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
  • 20Gastroenterology, Kettering General Hospital NHS Foundation Trust, Kettering, UK.
  • 21Roche Diagnostics GmbH, Mannheim, Baden-Württemberg, Germany.
  • 22IBD Unit - Gastroenterology, Hull University Teaching Hospitals NHS Trust, Hull, UK.
  • 23Hull York Medical School, University of Hull, Hull, UK.
  • 24Gastroenterology, Western General Hospital, Edinburgh, Edinburgh, UK.
  • 25The University of Edinburgh Centre for Genomic and Experimental Medicine, Edinburgh, UK.
  • 26Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • 27Gastroenterology, Imperial College Healthcare NHS Trust, London, UK.
  • 28Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK tariq.ahmad1@nhs.net.

#Contributed equally.

Abstract

Objective: Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine.

Design: Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3-10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine.

Results: Geometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn's disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine.

Conclusion: Infliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab.

Trial registration number: ISRCTN45176516.

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