PT - JOURNAL ARTICLE AU - Nicholas A Kennedy AU - James R Goodhand AU - Claire Bewshea AU - Rachel Nice AU - Desmond Chee AU - Simeng Lin AU - Neil Chanchlani AU - Jeffrey Butterworth AU - Rachel Cooney AU - Nicholas M Croft AU - Ailsa L Hart AU - Peter M Irving AU - Klaartje B Kok AU - Christopher A Lamb AU - Jimmy K Limdi AU - Jonathan Macdonald AU - Dermot PB McGovern AU - Shameer J Mehta AU - Charles D Murray AU - Kamal V Patel AU - Richard CG Pollok AU - Timothy Raine AU - Richard K Russell AU - Christian P Selinger AU - Philip J Smith AU - Jack Bowden AU - Timothy J McDonald AU - Charlie W Lees AU - Shaji Sebastian AU - Nicholas Powell AU - Tariq Ahmad ED - , TI - Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab AID - 10.1136/gutjnl-2021-324388 DP - 2021 May 01 TA - Gut PG - 865--875 VI - 70 IP - 5 4099 - http://gut.bmj.com/content/70/5/865.short 4100 - http://gut.bmj.com/content/70/5/865.full SO - Gut2021 May 01; 70 AB - Objective Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections.Design Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020.Results Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2–5.6) vs 37.0 (15.2–76.1), p<0.0001).Conclusions Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy.Trial registration number ISRCTN45176516.Data are available on 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.