Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab.
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.
Author
Kennedy, Nicholas A
Goodhand, James R
Bewshea, Claire
Nice, Rachel
Chee, Desmond
Lin, Simeng
Chanchlani, Neil
Butterworth, Jeffrey
Cooney, Rachel
Croft, Nicholas M
Hart, Ailsa L
Irving, Peter M
Kok, Klaartje B
Lamb, Christopher A
Limdi, Jimmy K
MacDonald, Jonathan
McGovern, Dermot Pb
Mehta, Shameer J
Murray, Charles D
Patel, Kamal V
Pollok, Richard Cg
Raine, Timothy
Russell, Richard K
Selinger, Christian P
Smith, Philip J
Bowden, Jack
McDonald, Timothy J
Lees, Charlie W
Sebastian, Shaji
Powell, Nicholas
Ahmad, Tariq
Goodhand, James R
Bewshea, Claire
Nice, Rachel
Chee, Desmond
Lin, Simeng
Chanchlani, Neil
Butterworth, Jeffrey
Cooney, Rachel
Croft, Nicholas M
Hart, Ailsa L
Irving, Peter M
Kok, Klaartje B
Lamb, Christopher A
Limdi, Jimmy K
MacDonald, Jonathan
McGovern, Dermot Pb
Mehta, Shameer J
Murray, Charles D
Patel, Kamal V
Pollok, Richard Cg
Raine, Timothy
Russell, Richard K
Selinger, Christian P
Smith, Philip J
Bowden, Jack
McDonald, Timothy J
Lees, Charlie W
Sebastian, Shaji
Powell, Nicholas
Ahmad, Tariq
Citations
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Date
2021-03-22
Type
Article
Other
Other
Subject
Biochemistry, Paediatrics, Microbiology. Immunology
Collections
Citation
Kennedy NA, Goodhand JR, Bewshea C, Nice R, Chee D, Lin S, Chanchlani N, Butterworth J, Cooney R, Croft NM, Hart AL, Irving PM, Kok KB, Lamb CA, Limdi JK, Macdonald J, McGovern DP, Mehta SJ, Murray CD, Patel KV, Pollok RC, Raine T, Russell RK, Selinger CP, Smith PJ, Bowden J, McDonald TJ, Lees CW, Sebastian S, Powell N, Ahmad T; Contributors to the CLARITY IBD study. Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab. Gut. 2021 May;70(5):865-875. doi: 10.1136/gutjnl-2021-324388. Epub 2021 Mar 22
Journal / Source Title
Gut
DOI
10.1136/gutjnl-2021-324388
PMID
33753421
Publisher
British Medical Association
Publisher’s URL
http://gut.bmj.com/