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

Gut. 2021 Oct;70(10):1884-1893. doi: 10.1136/gutjnl-2021-324789. Epub 2021 Apr 26.

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.

Keywords: BNT162b2; CLARITY; COVID-19; ChAdOx1 nCoV-19; TNF; autoimmune disease; inflammatory bowel disease; inflammatory diseases; infliximab; vaccine; vedolizumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antibodies, Viral / immunology
  • Antibody Formation / immunology
  • BNT162 Vaccine
  • COVID-19 / immunology
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / administration & dosage
  • COVID-19 Vaccines / immunology*
  • ChAdOx1 nCoV-19
  • Female
  • Gastrointestinal Agents / adverse effects*
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Infliximab / therapeutic use*
  • Male
  • Middle Aged
  • SARS-CoV-2
  • Serologic Tests

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Gastrointestinal Agents
  • vedolizumab
  • ChAdOx1 nCoV-19
  • Infliximab
  • BNT162 Vaccine

Associated data

  • ISRCTN/ISRCTN45176516