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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Related collections

Most cited references 34

Record: found
Abstract: found
Article: not found

A brief measure for assessing generalized anxiety disorder: the GAD-7.

Robert L Spitzer, Kurt Kroenke, Janet B W Williams … (2006)

Generalized anxiety disorder (GAD) is one of the most common mental disorders; however, there is no brief clinical measure for assessing GAD. The objective of this study was to develop a brief self-report scale to identify probable cases of GAD and evaluate its reliability and validity. A criterion-standard study was performed in 15 primary care clinics in the United States from November 2004 through June 2005. Of a total of 2740 adult patients completing a study questionnaire, 965 patients had a telephone interview with a mental health professional within 1 week. For criterion and construct validity, GAD self-report scale diagnoses were compared with independent diagnoses made by mental health professionals; functional status measures; disability days; and health care use. A 7-item anxiety scale (GAD-7) had good reliability, as well as criterion, construct, factorial, and procedural validity. A cut point was identified that optimized sensitivity (89%) and specificity (82%). Increasing scores on the scale were strongly associated with multiple domains of functional impairment (all 6 Medical Outcomes Study Short-Form General Health Survey scales and disability days). Although GAD and depression symptoms frequently co-occurred, factor analysis confirmed them as distinct dimensions. Moreover, GAD and depression symptoms had differing but independent effects on functional impairment and disability. There was good agreement between self-report and interviewer-administered versions of the scale. The GAD-7 is a valid and efficient tool for screening for GAD and assessing its severity in clinical practice and research.

0 comments Cited 6973 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The REDCap consortium: Building an international community of software platform partners

Paul Harris, Robert Taylor, Brenda Minor … (2019)

The Research Electronic Data Capture (REDCap) data management platform was developed in 2004 to address an institutional need at Vanderbilt University, then shared with a limited number of adopting sites beginning in 2006. Given bi-directional benefit in early sharing experiments, we created a broader consortium sharing and support model for any academic, non-profit, or government partner wishing to adopt the software. Our sharing framework and consortium-based support model have evolved over time along with the size of the consortium (currently more than 3200 REDCap partners across 128 countries). While the "REDCap Consortium" model represents only one example of how to build and disseminate a software platform, lessons learned from our approach may assist other research institutions seeking to build and disseminate innovative technologies.

0 comments Cited 5072 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

OpenSAFELY: factors associated with COVID-19 death in 17 million patients

Elizabeth J Williamson, Alex J Walker, Krishnan Bhaskaran … (2020)

COVID-19 has rapidly impacted on mortality worldwide. 1 There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19 related deaths. COVID-19 related death was associated with: being male (hazard ratio 1.59, 95%CI 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared to people with white ethnicity, black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.29-1.69 and 1.45, 1.32-1.58 respectively). We have quantified a range of clinical risk factors for COVID-19 related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly.

0 comments Cited 2928 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Gut

Journal ID (iso-abbrev): Gut

Journal ID (hwp): gutjnl

Journal ID (publisher-id): gut

Title: Gut

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Print): 0017-5749

ISSN (Electronic): 1468-3288

Publication date (Print): March 2021

Publication date (Electronic): 22 March 2021

Electronic Location Identifier: gutjnl-2021-324388

Affiliations

[1 ] departmentDepartment of Gastroenterology , Royal Devon and Exeter NHS Foundation Trust , Exeter, UK

[2 ] departmentExeter Inflammatory Bowel Disease and Pharmacogenetics Research Group , University of Exeter , Exeter, UK

[3 ] departmentDepartment of Biochemistry, Exeter Clinical Laboratory International , Royal Devon and Exeter NHS Foundation Trust , Exeter, UK

[4 ] departmentDepartment of Gastroenterology , Shrewsbury and Telford Hospital NHS Trust , Shrewsbury, UK

[5 ] departmentDepartment of Gastroenterology , University Hospitals Birmingham NHS Foundation Trust , Birmingham, UK

[6 ] departmentDepartment of Paediatric Gastroenterology , Royal London Hospital, Barts Health NHS Trust , London, UK

[7 ] departmentCentre for Immunobiology, Blizard Institute , Barts and the London School of Medicine, Queen Mary University of London , London, UK

[8 ] departmentDepartment of Gastroenterology , St Mark's Hospital and Academic Institute , Harrow, London, UK

[9 ] departmentDepartment of Gastroenterology , Guy's and St Thomas' NHS Foundation Trust , London, UK

[10 ] departmentSchool of Immunology & Microbial Sciences , King's College London , London, UK

[11 ] departmentDepartment of Gastroenterology , Royal London Hospital, Barts Health NHS Trust , London, UK

[12 ] departmentDepartment of Gastroenterology , Newcastle Upon Tyne Hospitals NHS Foundation Trust , Newcastle Upon Tyne, UK

[13 ] departmentTranslational & Clinical Research Institute, Faculty of Medical Sciences , Newcastle University , Newcastle upon Tyne, UK

[14 ] departmentDepartment of Gastroenterology , Pennine Acute Hospitals NHS Trust , Manchester, UK

[15 ] departmentFaculty of Biology, Medicine & Health , University of Manchester , Manchester, UK

[16 ] departmentDepartment of Gastroenterology, Queen Elizabeth University Hospital , NHS Greater Glasgow and Clyde , Glasgow, UK

[17 ] departmentF. Widjaja Foundation Inflammatory Bowel and Immunology Research Institute , Cedars-Sinai Medical Center , Los Angeles, California, USA

[18 ] departmentDepartment of Gastroenterology , University College London Hospitals NHS Foundation Trust , London, UK

[19 ] departmentDepartment of Gastroenterology , Royal Free London NHS Foundation Trust , London, UK

[20 ] departmentDepartment of Gastroenterology , St George's University Hospitals NHS Foundation Trust , London, UK

[21 ] departmentInstitute for Infection and Immunity , University of London , London, UK

[22 ] departmentDepartment of Gastroenterology , Cambridge University Hospitals NHS Foundation Trust , Cambridge, UK

[23 ] departmentDepartment of Paediatric Gastroenterology , Royal Hospital for Sick Children, NHS Lothian , Edinburgh, UK

[24 ] departmentDepartment of Gastroenterology , Leeds Teaching Hospitals NHS Trust , Leeds, UK

[25 ] departmentDepartment of Gastroenterology , Liverpool University Hospitals NHS Foundation Trust , Liverpool, UK

[26 ] departmentMedical School , University of Exeter , Exeter, UK

[27 ] departmentDepartment of Gastroenterology , Western General Hospital, NHS Lothian , Edinburgh, UK

[28 ] departmentInstitute of Genetic and Molecular Medicine , University of Edinburgh , Edinburgh, UK

[29 ] departmentDepartment of Gastroenterology , Hull University Teaching Hospitals NHS Trust , Hull, UK

[30 ] departmentDivision of Digestive Diseases, Faculty of Medicine , Imperial College London , London, UK

[31 ] departmentDepartment of Metabolism, Digestion and Reproduction , Imperial College London , London, UK

Author notes

[Correspondence to ] Dr Tariq Ahmad, Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, Devon, UK; tariq.ahmad1@ 123456nhs.net

Author information

Nicholas A Kennedy http://orcid.org/0000-0003-4368-1961

James R Goodhand http://orcid.org/0000-0003-3112-376X

Claire Bewshea http://orcid.org/0000-0002-0965-9587

Desmond Chee http://orcid.org/0000-0003-3473-9447

Simeng Lin http://orcid.org/0000-0002-4201-4879

Neil Chanchlani http://orcid.org/0000-0003-0207-6706

Rachel Cooney http://orcid.org/0000-0003-3710-157X

Nicholas M Croft http://orcid.org/0000-0002-1519-6435

Ailsa L Hart http://orcid.org/0000-0002-7141-6076

Peter M Irving http://orcid.org/0000-0003-0972-8148

Klaartje B Kok http://orcid.org/0000-0002-5942-9149

Christopher A Lamb http://orcid.org/0000-0002-7271-4956

Jimmy K Limdi http://orcid.org/0000-0002-1039-6251

Dermot PB McGovern http://orcid.org/0000-0001-5621-759X

Shameer J Mehta http://orcid.org/0000-0002-7002-293X

Charles D Murray http://orcid.org/0000-0001-6736-1546

Kamal V Patel http://orcid.org/0000-0003-2611-4260

Richard CG Pollok http://orcid.org/0000-0001-6452-6763

Timothy Raine http://orcid.org/0000-0002-5855-9873

Richard K Russell http://orcid.org/0000-0001-7398-4926

Christian P Selinger http://orcid.org/0000-0003-2022-5859

Philip J Smith http://orcid.org/0000-0003-1568-3978

Jack Bowden http://orcid.org/0000-0003-2628-3304

Timothy J McDonald http://orcid.org/0000-0003-3559-6660

Charlie W Lees http://orcid.org/0000-0002-0732-8215

Shaji Sebastian http://orcid.org/0000-0002-3670-6545

Nicholas Powell http://orcid.org/0000-0003-3231-6950

Tariq Ahmad http://orcid.org/0000-0002-6058-5528

Article

Publisher ID: gutjnl-2021-324388

DOI: 10.1136/gutjnl-2021-324388

PMC ID: 7992387

PubMed ID: 33753421

SO-VID: eccbea87-0b69-429b-9754-fecaef9c9fc4

License:

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.

History

Date received : 10 February 2021

Date revision received : 17 February 2021

Date accepted : 18 February 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100007013, F. Hoffmann-La Roche;

Award ID: N/A

Funded by: Hull University Teaching Hospital NHS Trust;

Award ID: N/A

Funded by: http://dx.doi.org/10.13039/100005614, Biogen;

Award ID: N/A

Funded by: FundRef http://dx.doi.org/10.13039/100010780, Celltrion Healthcare;

Award ID: N/A

Funded by: Galapagos NV;

Award ID: N/A

Funded by: FundRef http://dx.doi.org/10.13039/100009745, Royal Devon and Exeter NHS Foundation Trust;

Award ID: N/A

Custom metadata

access-type free

special-feature press-release

ScienceOpen disciplines: Gastroenterology & Hepatology

Keywords: inflammatory bowel disease,autoimmune disease,covid-19,inflammatory diseases,infliximab,vedoluzimab,clarity

Data availability:

ScienceOpen disciplines: Gastroenterology & Hepatology

Keywords: inflammatory bowel disease, autoimmune disease, covid-19, inflammatory diseases, infliximab, vedoluzimab, clarity

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

Read this article at

Abstract

Objective

Design

Results

Conclusions

Trial registration number

Related collections

UCL: Covid-19 Research

Most cited references 34

A brief measure for assessing generalized anxiety disorder: the GAD-7.

The REDCap consortium: Building an international community of software platform partners

OpenSAFELY: factors associated with COVID-19 death in 17 million patients

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 367

Cited by 82

Most referenced authors 1,135