Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab

Nicholas A. Kennedy, James R. Goodhand, Claire Bewshea, Rachel Nice, Desmond Chee, Simeng Lin, Neil Chanchlani, Jeffrey Butterworth, Rachel Cooney, Nicholas M. Croft, Ailsa L. Hart, Peter M. Irving, Klaartje B. Kok, Christopher A. Lamb, Jimmy K. Limdi, Jonathan MacDonald, Dermot P. B. McGovern, Shameer J. Mehta, Charles D. Murray, Kamal V. PatelRichard C. G. Pollok, Timothy Raine, Richard K. Russell, Christian P. Selinger, Philip J. Smith, Jack Bowden, Timothy J. McDonald, Charlie W. Lees, Shaji Sebastian, Nicholas Powell, Tariq Ahmad (Lead / Corresponding author),

Research output: Contribution to journalArticlepeer-review

131 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)865-875
Number of pages11
JournalGut
Volume70
Issue number5
Early online date22 Mar 2021
DOIs
Publication statusPublished - 1 May 2021

Keywords

  • autoimmune disease
  • clarity
  • COVID-19
  • inflammatory bowel disease
  • inflammatory diseases
  • infliximab
  • vedoluzimab

ASJC Scopus subject areas

  • Gastroenterology

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