Journal Article

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

Hamilton, Benjamin, Jochum, Simon, Lees, Charlie W, Sebastian, Shaji, Powell, Nick, Chee, Desmond, McDonald, Timothy J, Nice, Rachel, Kamperidis, Nikolaos, Ahmad, Tariq, Kennedy, Nicholas A, Goodhand, James R, Cummings, JR Fraser, Raine, Tim, Verma, Ajay Mark, Lin, Simeng, Chanchlani, Neil, Pollok, Richard CG, Fraser, Aileen, Lamb, Christopher Andrew, Mehta, Shameer, Kok, Klaartje B, Smith, Philip J, Macdonald, Jonathan, Bewshea, Claire, Irving, Peter M

2021

Overview

ObjectiveDelayed 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.DesignAntibody 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.ResultsGeometric 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.ConclusionInfliximab 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.

• Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adult / Antibodies / Antibodies, Monoclonal, Humanized - therapeutic use / Antibodies, Viral - immunology / Antibody Formation - immunology / Antigens / autoimmune disease / BNT162 Vaccine / BNT162b2 / ChAdOx1 nCoV-19 / CLARITY / Coronaviruses / COVID-19 / COVID-19 - immunology / COVID-19 - prevention & control / COVID-19 vaccines / COVID-19 Vaccines - administration & dosage / COVID-19 Vaccines - immunology / Crohn's disease / Dosage / Drug dosages / Ethnicity / Female / Gastrointestinal Agents - adverse effects / Humans / Immunoassay / Immunogenicity / Immunomodulation / Infections / Inflammatory Bowel Disease / Inflammatory bowel diseases / Inflammatory Bowel Diseases - drug therapy / inflammatory diseases / Infliximab / Infliximab - therapeutic use / Laboratories / Male / Middle Aged / Monoclonal antibodies / Population / Proteins / SARS-CoV-2 / Seroconversion / Serologic Tests / Serology / Severe acute respiratory syndrome coronavirus 2 / TNF / TNF inhibitors / Tumor necrosis factor-α / vaccine / Vaccines / vedolizumab