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Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab.
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.
  • Kennedy NA; Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Goodhand JR; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Bewshea C; Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Nice R; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Chee D; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Lin S; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Chanchlani N; Department of Biochemistry, Exeter Clinical Laboratory International, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Butterworth J; Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Cooney R; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Croft NM; Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Hart AL; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Irving PM; Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Kok KB; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Lamb CA; Department of Gastroenterology, Shrewsbury and Telford Hospital NHS Trust, Shrewsbury, UK.
  • Limdi JK; Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • Macdonald J; Department of Paediatric Gastroenterology, Royal London Hospital, Barts Health NHS Trust, London, UK.
  • McGovern DP; Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK.
  • Mehta SJ; Department of Gastroenterology, St Mark's Hospital and Academic Institute, Harrow, London, UK.
  • Murray CD; Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
  • Patel KV; School of Immunology & Microbial Sciences, King's College London, London, UK.
  • Pollok RC; Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK.
  • Raine T; Department of Gastroenterology, Royal London Hospital, Barts Health NHS Trust, London, UK.
  • Russell RK; Department of Gastroenterology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
  • Selinger CP; Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
  • Smith PJ; Department of Gastroenterology, Pennine Acute Hospitals NHS Trust, Manchester, UK.
  • Bowden J; Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK.
  • McDonald TJ; Department of Gastroenterology, Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK.
  • Lees CW; F. Widjaja Foundation Inflammatory Bowel and Immunology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Sebastian S; Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK.
  • Powell N; Department of Gastroenterology, Royal Free London NHS Foundation Trust, London, UK.
  • Ahmad T; Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK.
Gut ; 70(5): 865-875, 2021 05.
Article in English | MEDLINE | ID: covidwho-1388530
Semantic information from SemMedBD (by NLM)
1. infliximab TREATS Patients
Subject
infliximab
Predicate
TREATS
Object
Patients
2. Viral Vaccines PREDISPOSES Respiratory Tract Infections
Subject
Viral Vaccines
Predicate
PREDISPOSES
Object
Respiratory Tract Infections
3. Antibody Formation PROCESS_OF Participant
Subject
Antibody Formation
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PROCESS_OF
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Participant
4. infliximab compared_with vedolizumab
Subject
infliximab
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compared_with
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vedolizumab
5. infliximab TREATS Participant
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infliximab
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TREATS
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6. vedolizumab TREATS Participant
Subject
vedolizumab
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TREATS
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Participant
7. COVID-19 PROCESS_OF Patients
Subject
COVID-19
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PROCESS_OF
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Patients
8. COVID-19 AFFECTS Necrosis
Subject
COVID-19
Predicate
AFFECTS
Object
Necrosis
9. infliximab TREATS Patients
Subject
infliximab
Predicate
TREATS
Object
Patients
10. Viral Vaccines PREDISPOSES Respiratory Tract Infections
Subject
Viral Vaccines
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PREDISPOSES
Object
Respiratory Tract Infections
11. Antibody Formation PROCESS_OF Participant
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Antibody Formation
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PROCESS_OF
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12. infliximab compared_with vedolizumab
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infliximab
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compared_with
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vedolizumab
13. infliximab TREATS Participant
Subject
infliximab
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TREATS
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14. vedolizumab TREATS Participant
Subject
vedolizumab
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TREATS
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Participant
15. COVID-19 PROCESS_OF Patients
Subject
COVID-19
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PROCESS_OF
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Patients
16. COVID-19 AFFECTS Necrosis
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COVID-19
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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 α4ß7 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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Gastrointestinal Agents / Inflammatory Bowel Diseases / Infliximab / SARS-CoV-2 / Antibodies, Viral / Antibody Formation Type of study: Controlled clinical trial / Diagnostic study / Observational study / Randomized controlled trials / Risk factors Topics: Long Covid / Vaccines Limits: Adult / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Journal: Gut Year: 2021 Document Type: Article Affiliation country: GUTJNL-2021-324388

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Gastrointestinal Agents / Inflammatory Bowel Diseases / Infliximab / SARS-CoV-2 / Antibodies, Viral / Antibody Formation Type of study: Controlled clinical trial / Diagnostic study / Observational study / Randomized controlled trials / Risk factors Topics: Long Covid / Vaccines Limits: Adult / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Journal: Gut Year: 2021 Document Type: Article Affiliation country: GUTJNL-2021-324388