Abstract

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.

Rights

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. https://bmj.com/coronavirus/usage

Cite as

Kennedy, N., Goodhand, J., Bewshea, C., Nice, R., Chee, D., Lin, S., Chanchlani, N., Butterworth, J., Cooney, R., Croft, N., Hart, A., Irving, P., Kok, K., Lamb, C., Limdi, J., MacDonald, J., McGovern, D., Mehta, S., Murray, C., Patel, K., Pollok, R., Raine, T., Russell, R., Selinger, C., Smith, P., Bowden, J., McDonald, T., Lees, C., Sebastian, S., Powell, N. & Ahmad, T. 2021, 'Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab', Gut, 70(5), pp. 865-875. http://dx.doi.org/10.1136/gutjnl-2021-324388

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Last updated: 16 June 2022
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