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  • Combination therapy of infliximab and thiopurines, but not monotherapy with infliximab or vedolizumab, is associated with attenuated IgA and neutralisation responses to SARS-CoV-2 in inflammatory bowel disease

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Combination therapy of infliximab and thiopurines, but not monotherapy with infliximab or vedolizumab, is associated with attenuated IgA and neutralisation responses to SARS-CoV-2 in inflammatory bowel disease
  1. Judith Wellens1,2,
  2. Matthew Edmans2,3,
  3. Uri Obolski4,5,
  4. Colleen GC McGregor2,
  5. Peter Simmonds3,
  6. Marc Turner6,
  7. Lisa Jarvis6,
  8. Donal Skelly3,7,
  9. Susanna Dunachie8,9,10,
  10. Eleanor Barnes2,3,
  11. David W Eyre8,11,
  12. Jean-Frederic Colombel12,
  13. Serre-Yu Wong13,
  14. Paul Klenerman2,3,
  15. James O Lindsay14,
  16. Jack Satsangi2,
  17. Craig P Thompson15,16
  1. 1 Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
  2. 2 Translational Gastroenterology Unit, University of Oxford, Oxford, UK
  3. 3 Nuffield Department of Medicine, University of Oxford, Oxford, UK
  4. 4 School of Public Health, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
  5. 5 Porter School of Environmental and Earth Sciences, Faculty of Exact Sciences, Tel-Aviv University, Tel-Aviv, Israel
  6. 6 National Microbiology Reference Unit, Scottish National Blood Transfusion Service, Edinburgh, Edinburgh, UK
  7. 7 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  8. 8 Department of Microbiology/Infectious Diseases, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK
  9. 9 Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
  10. 10 Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
  11. 11 Nuffield Department of Population Health, University of Oxford, Oxford, UK
  12. 12 Department of Gastroenterology, Mount Sinai School of Medicine, New York, New York, USA
  13. 13 The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA
  14. 14 Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK
  15. 15 Warwick Medical School, University of Warwick, Coventry, UK
  16. 16 Department of Zoology, University of Oxford, Oxford, UK
  1. Correspondence to Dr Craig P Thompson, University of Warwick Warwick Medical School, Coventry CV4 7HL, UK; craigpeterthompson{at}gmail.com

https://doi.org/10.1136/gutjnl-2021-326312

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    The effect of immunomodulator and biological therapy for IBD on the immune response to SARS-CoV-2 is of substantial interest to patients and clinicians worldwide. The CLARITY IBD study recently reported attenuated serological responses in patients with IBD treated with infliximab in comparison with vedolizumab,1 with the effect greatest in those on infliximab/thiopurine combination therapy. Independently, the global SECURE-IBD registry highlighted that infliximab/thiopurine combination therapy, but not infliximab or vedolizumab monotherapies, was associated with more severe clinical outcomes upon SARS-CoV-2 infection.2 3

    However, these studies have not addressed treatment effects on neutralising antibody responses, which are associated with protection to SARS-CoV-2; nor have they analysed the range of serological signatures that may influence clinical outcomes.4 5

    To answer these questions, we performed an extended analysis of serological responses to SARS-CoV-2 infection in patients with seropositive IBD treated with either infliximab or vedolizumab monotherapy, or infliximab/thiopurine combination therapy (figures 1 and 2; online supplemental material). Blood samples were collected from consenting patients attending infusion centres in Oxford and London between May and December 2020. Sera were initially screened by Abbott assay for SARS-CoV-2 antibody responses.6 Serological reactivity profiles in positive samples were compared with those from healthy adult controls seropositive in the same assay7 (online supplemental table 1).

    Supplemental material

    [gutjnl-2021-326312supp001.pdf]

    Supplemental material

    [gutjnl-2021-326312supp002.pdf]

    Figure 1

    IgG responses to whole spike, receptor binding domain and nucleocapsid following SARS-CoV-2 detection in patients with IBD and healthy controls. (A) IgG SARS-CoV-2 spike responses measured by high-throughput …

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    Footnotes

    • Twitter @ColleenMcGreg15

    • JW and ME contributed equally.

    • Contributors ME, JW ran experiments. ME, JW, UO, CPT, JS S-YW, J-FC, PK, SD, EB, DE, DS, JL analysed data. ME, JW, CPT, JS, PS, LJ, MT, PK, CM, SD wrote paper. SD, PK, CGM, CPT, JS designed the study.

    • Funding This study was funded by Leona M. and Harry B. Helmsley Charitable Trust (2107–04731), National Institute for Health Research (COV19-RECPLAS).

    • Competing interests JS has received lecture fees from Takeda and from the Falk Foundation.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.