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  • Maintenance therapy with infliximab or vedolizumab in IBD is not associated with increased SARS-CoV-2 seroprevalence: UK experience in the 2020 pandemic

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Maintenance therapy with infliximab or vedolizumab in IBD is not associated with increased SARS-CoV-2 seroprevalence: UK experience in the 2020 pandemic
  1. Colleen GC McGregor1,
  2. Alex Adams1,
  3. Ross Sadler2,
  4. Carolina V Arancibia-Cárcamo1,
  5. Rebecca Palmer1,
  6. Tim Ambrose1,
  7. Oliver Brain1,
  8. Alissa Walsh1,
  9. Paul Klenerman1,
  10. Simon PL Travis1,
  11. Nicholas M Croft3,4,
  12. James O Lindsay3,4,
  13. Jack Satsangi1
  1. 1 Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
  2. 2 Department of Laboratory Immunology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  3. 3 Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK
  4. 4 Departments of Gastroenterology and Paediatric Gastroenterology, Royal London Hospital, Barts Health NHS Trust, London, UK
  1. Correspondence to Dr Colleen GC McGregor, Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford OX3 9DU, UK; colleen.mcgregor{at}ndm.ox.ac.uk

https://doi.org/10.1136/gutjnl-2021-324116

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    We read with great interest the recent publication from Ungaro and colleagues,1 reporting the latest data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) registry. These data, while raising concerns regarding the use of thiopurine and corticosteroid therapy in the SARS-CoV-2 pandemic, also provide valuable reassurance that monotherapy with anticytokine therapies, in particular those directed against tumour necrosis factor (TNF), are not associated with adverse outcomes in patients with IBD developing COVID-19. It has been postulated that anticytokine therapies may ameliorate or abrogate the ‘cytokine storm’ associated with severe COVID-19,2 with anti-IL6 strategies now approved for use.3

    We have assessed the SARS-CoV-2 antibody seroprevalence in patients with IBD, receiving either intravenous anti-TNF therapy, or anti-integrin therapy, during the first wave of the pandemic in the UK.

    Sera from 640 patients attending for maintenance infliximab or vedolizumab infusions between April and June 2020 at the John Radcliffe Hospital (Oxford, UK) and Royal London Hospital (London, UK) were tested using the Abbott SARS-CoV-2 IgG assay. Adults (180) and paediatric (56) patients were included from London. Demographic and clinical data are summarised (online supplemental tables 1, 2). Key differences between the Oxford and London adult cohorts included ethnicity, smoking, comorbidities, disease type, concomitant thiopurines and biologic; in our data set, patients attending Royal London Hospital had significantly greater evidence for deprivation than Oxford (deprivation score 4 (3–6.3) vs 8 (6–9.3), p<0.001). Seroprevalence data were compared with available data from a contemporaneous healthy healthcare worker (HCW) study in Oxford4 and from a Public Health England seroprevalence study in unselected paediatric patients attending the Royal London Children’s Hospital.

    Supplemental material

    We report no increase in overall SARS-CoV-2 seropositivity in patients with IBD on biologics compared with controls. 12/404 (3.0%) patients tested positive for SARS-CoV-2 antibodies in Oxford. A higher seroprevalence rate was reported in London patients, 13/180 (7.2%) for adults (p≤0.0001 vs Oxford patients) and 7/56 (12.5%) for children (table 1). Seroprevalence rates in adult IBD cohorts were lower than rates reported in local healthy controls. Seroprevalence in all Oxford HCW of 10.6% and in non-patient facing HCW (6.1%)4 were higher than in patients (p<0.00001 and p<0.0154, respectively). Seroprevalence rates of the London paediatric control group were comparable to patients, 13.6% (54/396, median age 13.0 years (8.1–16.0), male 49%).

    View this table:
    Table 1

    (A). Overall SARS-CoV-2 seroprevalence per cohort. (B). Seropositivity versus biologic and IBD diagnoses. (C). Seropositivity versus concomitant thiopurine therapy (D). Univariable relationships between clinical, socioeconomic and demographic factors with SARS-CoV-2 seropositivity

    On univariate analyses, there were no associations of SARS-CoV-2 positive patients with baseline characteristics, including ethnicity or deprivation status or concomitant thiopurine use (table 1, online supplemental table 3). In Oxford, a trend towards lower seropositivity was observed in patients on infliximab versus vedolizumab (1.1% vs 4.4%); only two anti-TNF treated patients were seropositive (table 1). These trends were not observed in adults or children in London. Concomitant budesonide or 5-aminosalicylic acid use was associated with higher seropositivity rates, although statistical significance was not reached.

    These seroprevalence data, the first reported from the UK during the pandemic, and the first analysis of a paediatric cohort undergoing biological therapies, complement the SECURE-IBD registry data, and also seroprevalence data from Germany5 and Italy.6 7 Together, these data sets provide substantial confidence to clinicians and patients in continuing biological therapy as monotherapy.

    Further data are keenly anticipated, with respect to susceptibility, severity of outcome, durability of serological response and effects on vaccination efficacy—these are the subjects of prospective analysis, both nationally in the UK-based CLARITY study8 and internationally by the SECURE-IBD and ICARUS-IBD Consortia.9 Results from these ongoing studies will be available within the next year and will be of great interest to clinicians and patients.

    Ethics statements

    Patient consent for publication

    Ethics approval

    Samples from Oxford patients were collected as a project (ref ORB 20/A054) under the ethical approval of the Oxford Radcliffe Biobank, a research tissue bank that has a favourable opinion from the Oxford C South Central REC, with reference 19/SC/0173. Samples from London patients were collected as a project under the ethical approval of the Digestive Disease Bioresource, Barts Health NHS Trust, a research tissue bank that has a favourable opinion from the Bromley REC, reference 15/LO/2127.

    Acknowledgments

    The authors wish to acknowledge the contributions to this work by Stephanie Jones, Jennifer Hollis, Sarah Cripps, Bessie Cipriano, Irish Lee, Kinnari Naik, Polychronis Kemos (QMUL), Ruth Ayling (Barts Health NHS Trust), David Eyre, Philippa Matthews, Oxford Radcliffe Biobank, James Chivenga and the TGU Biobank, Oxford Biomedical Research Centre, IBD Specialist & Research Nurses, TGU Investigators, Department of Clinical Biochemistry (John Radcliffe Hospital), and Clarissa Oeser (Public Health England). The authors also wish to thank Jean-Frederic Colombel and Serre-Yu Wong for helpful and constructive discussion.

    References

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    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Footnotes

    • Twitter @ColleenMcGreg15

    • Contributors CGCM—patient recruitment, analysis, drafting of manuscript. AA—analysis, drafting of manuscript. RS—sample analysis, manuscript revision. CVA-C, RP, TA, OB, AW, SPLT, JL, NC—patient recruitment, manuscript revision. PK—manuscript revision. JS—initiation of research, recruitment, drafting and revision of manuscript

    • Funding This work was partly supported by the Helmsley Trust as part of the ICARUS study [Grant Number 2107–04731]. CGCM is funded by an ECCO Pioneer Award. AA, CVA-C, AW, OB, and ST are funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC).

    • Disclaimer The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

    • Competing interests CVA-C has received grants from Celgene and Takeda outside the scope of the submitted work. AW reports personal fees outside the submitted work from Ferring Pharmaceuticals, Janssen, and Takeda. ST reports outside the submitted work receipt of grants/research support from AbbVie, Buhlmann, Celgene, IOIBD, Janssen, Lilly, Pfizer, Takeda, UCB, Vifor, and Norman Collisson Foundation; consulting fees from AbbVie, Allergan, Amgen, Arena, Asahi, Astellas, Biocare, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Buhlmann, Celgene, Chemocentryx, Cosmo, Enterome, Ferring, Giuliani SpA, GSK, Genentech, Immunocore, Immunometabolism, Indigo, Janssen, Lexicon, Lilly, Merck, MSD, Neovacs, Novartis, NovoNordisk, NPS Pharmaceuticals, Pfizer, Proximagen, Receptos, Roche, Sensyne, Shire, Sigmoid Pharma, SynDermix, Takeda, Theravance, Tillotts, Topivert, UCB, VHsquared, Vifor, and Zeria; speaker fees from AbbVie, Amgen, Biogen, Ferring, Janssen, Lilly, Pfizer, Shire, and Takeda; no stocks or share options. NMC reports research grants outside the submitted from Abbvie, Shire, Takeda, Pfizer, Eli Lilly, Jansenn, 4D Pharma, and lecture fees Abbvie. 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.