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Infliximab Is Associated with Attenuated Immunogenicity to Bnt162b2 and Chadox1 Ncov-19 SARS-Cov-2 Vaccines in Patients With

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Infliximab Is Associated with Attenuated Immunogenicity to Bnt162b2 and Chadox1 Ncov-19 SARS-Cov-2 Vaccines in Patients With Inflammatory bowel disease Original research Infliximab is associated with attenuated Gut: first published as 10.1136/gutjnl-2021-324789 on 26 April 2021. Downloaded from immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS- CoV-2 vaccines in patients with IBD 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 ,1,2 Contributors to the CLARITY IBD study ► Additional supplemental ABSTRACT material is published online Objective Delayed second dose SARS- CoV-2 vaccination Significance of this study only. To view, please visit the trades maximal effectiveness for a lower level of immunity journal online (http:// dx. doi. org/ What is already known on this subject? 10. 1136/ gutjnl- 2021- 324789). across more of the population. We investigated whether patients with inflammatory bowel disease treated with ► A growing number of countries, including the For numbered affiliations see UK, have opted to delay second SARS- CoV-2 end of article. infliximab have attenuated serological responses to a single dose of a SARS- CoV-2 vaccine. vaccine doses for all people, trading maximal effectiveness against a lower level of protective Correspondence to Design Antibody responses and seroconversion rates Dr Tariq Ahmad, in infliximab- treated patients (n=865) were compared immunity across more of the at- risk population. Gastroenterology, Royal Devon with a cohort treated with vedolizumab (n=428), a gut- Whether single doses of vaccines are effective http://gut.bmj.com/ and Exeter NHS Foundation in patients treated with antitumour necrosis selective anti- integrin α4β7 monoclonal antibody. Our Trust, Exeter, UK; factor (TNF) therapies is unknown. tariq. ahmad1@ nhs. net primary outcome was anti- SARS- CoV-2 spike (S) antibody We have previously shown in this cohort concentrations, measured using the Elecsys anti- SARS- CoV-2 ► that seroprevalence, seroconversion in PCR- NAK, SL and JRG contributed spike (S) antibody assay 3–10 weeks after vaccination, confirmed cases and the magnitude of anti- equally. in patients without evidence of prior infection. Secondary NP and TA contributed equally. SARS- CoV-2 antibodies following SARS- CoV-2 outcomes were seroconversion rates (defined by a cut- off of infection are reduced in infliximab- treated on September 23, 2021 by guest. Protected copyright. Received 29 March 2021 15 U/mL), and antibody responses following past infection or compared with vedolizumab- treated patients. Revised 8 April 2021 a second dose of the BNT162b2 vaccine. ► Two recent studies have reported that SARS- Accepted 10 April 2021 Results Geometric mean (SD) anti- SARS- CoV-2 antibody Published Online First CoV-2 spike (S) antibody responses are 26 April 2021 concentrations were lower in patients treated with infliximab impaired in patients with cancer and transplant than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs recipients treated with chemotherapy 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/ and antimetabolite immunosuppressants, mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our respectively. To date, no studies have multivariable models, antibody concentrations were lower assessed the effect of anti- TNF therapy gut. bmj. com in infliximab- treated compared with vedolizumab- treated on immunogenicity following SARS- CoV-2 patients who received the BNT162b2 (fold change (FC) 0.29 vaccination. (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- led to seroconversion in most patients. Delayed second white ethnicity was associated with higher, anti- SARS- CoV-2 dosing should be avoided in patients treated with antibody concentrations. Seroconversion rates after a single infliximab. © Author(s) (or their Trial registration number ISRCTN45176516. employer(s)) 2021. No dose of either vaccine were higher in patients with prior commercial re- use. See rights SARS- CoV-2 infection and after two doses of BNT162b2 and permissions. Published vaccine. by BMJ. Conclusion Infliximab is associated with attenuated INTRODUCTION To cite: Kennedy NA, Lin S, immunogenicity to a single dose of the BNT162b2 and Limited SARS- CoV-2 vaccine supplies and pressure Goodhand JR, et al. Gut ChAdOx1 nCoV-19 SARS- CoV-2 vaccines. Vaccination on critical care services have forced governments to 2021;70:1884–1893. after SARS-CoV -2 infection, or a second dose of vaccine, prioritise primary vaccination to vulnerable groups. 1884 Kennedy NA, et al. Gut 2021;70:1884–1893. doi:10.1136/gutjnl-2021-324789 Inflammatory bowel disease necrosis factor (TNF) drugs, such as infliximab and adalimumab, Significance of this study are the most frequently prescribed biopharmaceuticals used in the treatment of IMIDs. These drugs impair immunogenicity Gut: first published as 10.1136/gutjnl-2021-324789 on 26 April 2021. Downloaded from What are the new findings? following pneumococcal,6 influenza7 and hepatitis B8 vaccina- ► Anti- SARS- CoV-2 spike (S) antibody concentrations and rates tions and increase the risk of serious infection, most notably with of seroconversion were lower following primary vaccination respiratory pathogens.9 Conversely, vedolizumab, a gut- selective with both the BNT162b2 and ChAdOx1 nCoV-19 vaccines anti- integrin α4β7 monoclonal antibody, is not associated with in patients with inflammatory bowel disease treated with increased susceptibility to systemic infection or attenuated sero- infliximab compared with vedolizumab. logical responses to vaccination.10 ► Older age, immunomodulator use, Crohn’s disease (vs We have recently reported that seroprevalence, serocon- ulcerative colitis or inflammatory bowel disease unclassified), version in PCR-confirmed cases, and the magnitude of anti- and current smoking were associated with lower anti- SARS- SARS- CoV-2 antibodies following SARS- CoV-2 infection are CoV-2 antibody concentrations, irrespective of vaccine reduced in infliximab-treated compared with vedolizumab- type. Non- white ethnicity was associated with higher anti- treated patients.11 We hypothesised that, following at least a SARS- CoV-2 (S) antibody concentrations following primary single dose with BNT162b2 or ChAdOx1 nCoV-19 vaccine, vaccination with both vaccines. serological responses would be similarly impaired in patients ► Lowest rates of seroconversion were observed in treated with infliximab compared with vedolizumab arguing participants treated with infliximab in combination with an against delaying second doses in these patients. immunomodulator with both the BNT162b2 and ChAdOx1 nCoV-19 vaccines, whereas highest rates of seroconversion were seen in patients treated with vedolizumab monotherapy Objectives who received either vaccine. We aimed to define, in patients with IBD who had received a ► Antibody concentrations and seroconversion rates were COVID-19 vaccination, whether biological class and concomi- higher in patients with past SARS-CoV -2 infection prior to tant use of an immunomodulator impact: a single dose of either vaccine, and after two doses of the i. Anti- SARS- CoV-2 spike (S) antibody levels. BNT162b2 vaccine. ii. Rates of seroconversion. How might it impact on clinical practice in the foreseeable iii. Antibody responses in patients who had previously been in- future? fected with SARS-CoV -2 or who had two doses of vaccine. ► For patients treated with antitumour necrosis factor (TNF) therapy, particularly for those also treated with an METHODS immunomodulator, poor antibody responses to a single dose Patient and settings of vaccine exposes them to a potential increased risk of ImpaCt of bioLogic therApy on saRs- cov-2 Infection and immu- SARS- CoV-2 infection. niTY (CLARITY) IBD is a UK- wide, multicentre, prospective ► Higher rates of seroconversion in patients with two observational cohort study investigating the impact of inflix- http://gut.bmj.com/ exposures to SARS-CoV -2 antigen, even in the presence of imab and vedolizumab and/or concomitant immunomodu- TNF blockade, suggest that all patients receiving anti-TNF lators (azathioprine, mercaptopurine and methotrexate) on therapy should be prioritised for optimally timed second SARS-CoV -2 acquisition, illness and immunity in patients with doses. IBD. ► Until patients receive a second vaccine dose, they should Study methods have been described in detail previously.11 In consider that they are not protected from SARS-CoV -2 brief, consecutive patients were recruited at the time of atten- infection and continue to practice enhanced physical dance at infusion units from 92 National Health Service (NHS) on September 23, 2021 by guest. Protected copyright. distancing and shielding if appropriate. hospitals across the UK between 22 September 2020 and 23 ► Even after two antigen exposures, a small subset of patients December 2020 (online supplemental pp 2–17). The eligibility failed to mount an antibody response. Antibody testing and criteria were age 5 years and over, a diagnosis of IBD, and adapted vaccine schedules should be considered to protect current treatment with infliximab or vedolizumab for 6 weeks these at-risk patients. or more, with at least one dose of drug received in the previous 16 weeks. Patients were excluded if they had participated in a SARS- CoV-2 vaccine trial. In the UK, second vaccine doses have also been delayed, trading Follow- up visits were timed to coincide with biological infu- maximal effectiveness for a lower level of protective immunity sions and occurred approximately 8 weekly. Here, we report 1 across a greater proportion of the most at- risk population.
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