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Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD.
Kennedy, Nicholas A; Lin, Simeng; Goodhand, James R; Chanchlani, Neil; Hamilton, Benjamin; Bewshea, Claire; Nice, Rachel; Chee, Desmond; Cummings, Jr Fraser; Fraser, Aileen; Irving, Peter M; Kamperidis, Nikolaos; Kok, Klaartje B; Lamb, Christopher Andrew; Macdonald, Jonathan; Mehta, Shameer; Pollok, Richard Cg; Raine, Tim; Smith, Philip J; Verma, Ajay Mark; Jochum, Simon; McDonald, Timothy J; Sebastian, Shaji; Lees, Charlie W; Powell, Nick; Ahmad, Tariq.
  • Kennedy NA; Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Lin S; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Goodhand JR; Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Chanchlani N; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Hamilton B; Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Bewshea C; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Nice R; Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Chee D; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Cummings JF; Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Fraser A; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Irving PM; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Kamperidis N; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Kok KB; Biochemistry, Exeter Clinical Laboratory International, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Lamb CA; Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Macdonald J; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
  • Mehta S; Gastroenterology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
  • Pollok RC; Gastroenterology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.
  • Raine T; Gastroenterology, Guy's and St Thomas' Hospitals NHS Trust, London, UK.
  • Smith PJ; School of Immunology & Microbial Sciences, King's College London, London, UK.
  • Verma AM; Gastroenterology, St Marks Hospital and Academic Institute, London, UK, London, UK.
  • Jochum S; Gastroenterology, Barts and The London NHS Trust, London, UK.
  • McDonald TJ; Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry Blizard Institute, London, UK.
  • Sebastian S; Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Lees CW; Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Powell N; Gastroenterology, Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK.
  • Ahmad T; School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK.
Gut ; 70(10): 1884-1893, 2021 10.
Article in English | MEDLINE | ID: covidwho-1203979
Semantic information from SemMedBD (by NLM)
1. COVID-19 Vaccines TREATS Patients
Subject
COVID-19 Vaccines
Predicate
TREATS
Object
Patients
2. infliximab TREATS Inflammatory Bowel Diseases
Subject
infliximab
Predicate
TREATS
Object
Inflammatory Bowel Diseases
3. Inflammatory Bowel Diseases PROCESS_OF Patients
Subject
Inflammatory Bowel Diseases
Predicate
PROCESS_OF
Object
Patients
4. vedolizumab TREATS Cohort
Subject
vedolizumab
Predicate
TREATS
Object
Cohort
5. Antibody Formation PROCESS_OF Patients
Subject
Antibody Formation
Predicate
PROCESS_OF
Object
Patients
6. Vaccination TREATS Patients
Subject
Vaccination
Predicate
TREATS
Object
Patients
7. Antibodie PART_OF C5203676
Subject
Antibodie
Predicate
PART_OF
Object
C5203676
8. infliximab TREATS Patients
Subject
infliximab
Predicate
TREATS
Object
Patients
9. Patients LOCATION_OF Antibodie
Subject
Patients
Predicate
LOCATION_OF
Object
Antibodie
10. Antibodies COEXISTS_WITH infliximab
Subject
Antibodies
Predicate
COEXISTS_WITH
Object
infliximab
11. Antibodie ASSOCIATED_WITH C0010346
Subject
Antibodie
Predicate
ASSOCIATED_WITH
Object
C0010346
12. Vaccines TREATS COVID-19
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Vaccines
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TREATS
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COVID-19
13. COVID-19 PROCESS_OF Patients
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COVID-19
Predicate
PROCESS_OF
Object
Patients
14. Vaccines TREATS Patients
Subject
Vaccines
Predicate
TREATS
Object
Patients
15. Vaccines AFFECTS Seroconversion
Subject
Vaccines
Predicate
AFFECTS
Object
Seroconversion
16. COVID-19 Vaccines TREATS Patients
Subject
COVID-19 Vaccines
Predicate
TREATS
Object
Patients
17. infliximab TREATS Inflammatory Bowel Diseases
Subject
infliximab
Predicate
TREATS
Object
Inflammatory Bowel Diseases
18. Inflammatory Bowel Diseases PROCESS_OF Patients
Subject
Inflammatory Bowel Diseases
Predicate
PROCESS_OF
Object
Patients
19. vedolizumab TREATS Cohort
Subject
vedolizumab
Predicate
TREATS
Object
Cohort
20. Antibody Formation PROCESS_OF Patients
Subject
Antibody Formation
Predicate
PROCESS_OF
Object
Patients
21. Vaccination TREATS Patients
Subject
Vaccination
Predicate
TREATS
Object
Patients
22. Antibodies, Anti-Idiotypic PART_OF 2019 novel coronavirus
Subject
Antibodies, Anti-Idiotypic
Predicate
PART_OF
Object
2019 novel coronavirus
23. infliximab TREATS Patients
Subject
infliximab
Predicate
TREATS
Object
Patients
24. Patients LOCATION_OF Antibodies, Anti-Idiotypic
Subject
Patients
Predicate
LOCATION_OF
Object
Antibodies, Anti-Idiotypic
25. Antibodies COEXISTS_WITH infliximab
Subject
Antibodies
Predicate
COEXISTS_WITH
Object
infliximab
26. Antibodies, Anti-Idiotypic ASSOCIATED_WITH Crohn Disease
Subject
Antibodies, Anti-Idiotypic
Predicate
ASSOCIATED_WITH
Object
Crohn Disease
27. Vaccines TREATS COVID-19
Subject
Vaccines
Predicate
TREATS
Object
COVID-19
28. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
29. Vaccines TREATS Patients
Subject
Vaccines
Predicate
TREATS
Object
Patients
30. Vaccines AFFECTS Seroconversion
Subject
Vaccines
Predicate
AFFECTS
Object
Seroconversion
ABSTRACT

OBJECTIVE:

Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine.

DESIGN:

Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4ß7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3-10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine.

RESULTS:

Geometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn's disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine.

CONCLUSION:

Infliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab. TRIAL REGISTRATION NUMBER ISRCTN45176516.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Gastrointestinal Agents / Inflammatory Bowel Diseases / Infliximab / COVID-19 Vaccines / COVID-19 Type of study: Diagnostic study / Randomized controlled trials / Risk factors Topics: Vaccines Limits: Adult / Female / Humans / Male / Middle aged Language: English Journal: Gut Year: 2021 Document Type: Article Affiliation country: Gutjnl-2021-324789

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Gastrointestinal Agents / Inflammatory Bowel Diseases / Infliximab / COVID-19 Vaccines / COVID-19 Type of study: Diagnostic study / Randomized controlled trials / Risk factors Topics: Vaccines Limits: Adult / Female / Humans / Male / Middle aged Language: English Journal: Gut Year: 2021 Document Type: Article Affiliation country: Gutjnl-2021-324789