PT - JOURNAL ARTICLE AU - Nicholas A Kennedy AU - Simeng Lin AU - James R Goodhand AU - Neil Chanchlani AU - Benjamin Hamilton AU - Claire Bewshea AU - Rachel Nice AU - Desmond Chee AU - JR Fraser Cummings AU - Aileen Fraser AU - Peter M Irving AU - Nikolaos Kamperidis AU - Klaartje B Kok AU - Christopher Andrew Lamb AU - Jonathan Macdonald AU - Shameer Mehta AU - Richard CG Pollok AU - Tim Raine AU - Philip J Smith AU - Ajay Mark Verma AU - Simon Jochum AU - Timothy J McDonald AU - Shaji Sebastian AU - Charlie W Lees AU - Nick Powell AU - Tariq Ahmad ED - , TI - Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD AID - 10.1136/gutjnl-2021-324789 DP - 2021 Oct 01 TA - Gut PG - 1884--1893 VI - 70 IP - 10 4099 - http://gut.bmj.com/content/70/10/1884.short 4100 - http://gut.bmj.com/content/70/10/1884.full SO - Gut2021 Oct 01; 70 AB - 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.Data are available upon reasonable request. The study protocol including the statistical analysis plan is available at www.clarityibd.org. Individual participant deidentified 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.