Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform

Brian MacKenna, Nicholas A Kennedy, Amir Mehrkar, Anna Rowan, James Galloway, Julian Matthewman, Kathryn E Mansfield, Katie Bechman, Mark Yates, Jeremy Brown, Anna Schultze, Sam Norton, Alex J Walker, Caroline E Morton, David Harrison, Krishnan Bhaskaran, Christopher T Rentsch, Elizabeth Williamson, Richard Croker, Seb BaconGeorge Hickman, Tom Ward, Simon Davy, Amelia Green, Louis Fisher, William Hulme, Chris Bates, Helen J Curtis, John Tazare, Rosalind M Eggo, David Evans, Peter Inglesby, Jonathan Cockburn, Helen I McDonald, Laurie A Tomlinson, Rohini Mathur, Angel Y S Wong, Harriet Forbes, John Parry, Frank Hester, Sam Harper, Ian J Douglas, Liam Smeeth, Charlie W Lees, Stephen J W Evans, Ben Goldacre, Catherine H Smith, Sinéad M Langan

Research output: Contribution to journalArticlepeer-review

53 Citations (SciVal)

Abstract

BACKGROUND: The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies.

METHODS: We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate).

FINDINGS: We identified 17 672 065 adults; 1 163 438 adults (640 164 [55·0%] women and 523 274 [45·0%] men, and 827 457 [71·1%] of White ethnicity) had immune-mediated inflammatory diseases, and 16 508 627 people (8 215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] of White ethnicity) were included as the general population. Of 1 163 438 adults with immune-mediated inflammatory diseases, 19 119 (1·6%) received targeted immune-modifying therapy and 181 694 (15·6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1·23, 95% CI 1·20-1·27) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11-1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21-1·28; mediator-adjusted 1·16, 1·12-1·19) and hospital admission (confounder-adjusted 1·32, 1·29-1·35; mediator-adjusted 1·20, 1·17-1·23). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1·03, 95% CI 0·80-1·33), and after additionally adjusting for current glucocorticoid use (1·01, 0·78-1·30). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL‑23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1·68, 95% CI 1·11-2·56), with some attenuation after excluding people with haematological malignancies or organ transplants (1· 54, 0· 95- 2· 49).

INTERPRETATION: COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy.

FUNDING: UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.

Original languageEnglish
Pages (from-to)e490-e506
JournalThe Lancet Rheumatology
Volume4
Issue number7
Early online date9 Jun 2022
DOIs
Publication statusPublished - 9 Jun 2022
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the UK Medical Research Council (MRC; MR/V015737/1) and funded in part by the NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust and the Wellcome Trust (G205039/Z/16/Z). TPP and the North East Commissioning Support Unit North of England provided technical expertise and data infrastructure centre pro bono in the context of a national emergency. BG's work on better use of data in health care more broadly is currently funded in part by the NIHR Oxford Biomedical Research Centre, NIHR Applied Research Collaboration Oxford and Thames Valley, the Mohn-Westlake Foundation, NHS England, and the Health Foundation; all DataLab staff are supported by BG's grants on this work. LS reports grants from the Wellcome Trust, MRC, NIHR, UKRI, British Council, GlaxoSmithKline, British Heart Foundation, and Diabetes UK, outside this work. AS is employed by the London School of Hygiene & Tropical Medicine (LSHTM; UK) on a fellowship sponsored by GlaxoSmithKline. KBh holds a Sir Henry Dale fellowship jointly funded by the Wellcome Trust and the Royal Society. HIM is funded by the NIHR Health Protection Research Unit in Immunisation, a partnership between Public Health England and LSHTM. AYSW holds a fellowship from the British Heart Foundation. EW holds grants from the MRC. ID holds grants from NIHR and GlaxoSmithKline. RM holds a Sir Henry Wellcome Fellowship funded by the Wellcome Trust. HF holds a UKRI fellowship. RME is funded by HDR-UK and the MRC. SML was supported by a Wellcome Trust Senior Research Fellowship in Clinical Science (205039/Z/16/Z). The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funders. SML was also supported by Health Data Research UK (grant number: LOND1), which is funded by the MRC, the UK Engineering and Physical Sciences Research Council, the UK Economic and Social Research Council, the Department of Health and Social Care (England), the Chief Scientist Office of the Scottish Government Health and Social Care Directorates, the Health and Social Care Research and Development Division (Welsh Government), the Public Health Agency (Northern Ireland), the British Heart Foundation, and the Wellcome Trust. SML is an investigator on the European Union Horizon 2020-funded BIOMAP Consortium. CHS acknowledges support for this research from the NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust and the Psoriasis Association. CWL is funded by a UKRI Future Leaders Fellowship. LAT is funded by UKRI, the NIHR, and the MRC. The views expressed are those of the authors and not necessarily those of the NIHR, ICNARC, NHS England, Public Health England, or the UK Department of Health and Social Care. We are very grateful for all the support received from the TPP Technical Operations team throughout this work, and for generous assistance from the information governance and database teams at NHS England and NHSX. Additionally, the North East Commissioning Support Unit provided support on behalf of all Commissioning Support Unit to aggregate the high-cost drugs data. This study uses electronic health records, data are provided by patients and collected by the NHS as part of their care and support. This publication is based on data derived from the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database. The Case Mix Programme is the national, comparative audit of patient outcomes from adult critical care coordinated by ICNARC. We thank all the staff in the critical care units participating in the Case Mix Programme. For more information on the representativeness and quality of these data, please contact ICNARC. We are very grateful to Joe West from the University of Nottingham (UK) and Daniel Prieto-Alhambra from the University of Oxford (UK) for comments on an early version of the protocol.

Funding Information:
This work was supported by the UK Medical Research Council (MRC; MR/V015737/1) and funded in part by the NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust and the Wellcome Trust (G205039/Z/16/Z). TPP and the North East Commissioning Support Unit North of England provided technical expertise and data infrastructure centre pro bono in the context of a national emergency. BG's work on better use of data in health care more broadly is currently funded in part by the NIHR Oxford Biomedical Research Centre, NIHR Applied Research Collaboration Oxford and Thames Valley, the Mohn-Westlake Foundation, NHS England, and the Health Foundation; all DataLab staff are supported by BG's grants on this work. LS reports grants from the Wellcome Trust, MRC, NIHR, UKRI, British Council, GlaxoSmithKline, British Heart Foundation, and Diabetes UK, outside this work. AS is employed by the London School of Hygiene & Tropical Medicine (LSHTM; UK) on a fellowship sponsored by GlaxoSmithKline. KBh holds a Sir Henry Dale fellowship jointly funded by the Wellcome Trust and the Royal Society. HIM is funded by the NIHR Health Protection Research Unit in Immunisation, a partnership between Public Health England and LSHTM. AYSW holds a fellowship from the British Heart Foundation. EW holds grants from the MRC. ID holds grants from NIHR and GlaxoSmithKline. RM holds a Sir Henry Wellcome Fellowship funded by the Wellcome Trust. HF holds a UKRI fellowship. RME is funded by HDR-UK and the MRC. SML was supported by a Wellcome Trust Senior Research Fellowship in Clinical Science (205039/Z/16/Z). The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funders. SML was also supported by Health Data Research UK (grant number: LOND1), which is funded by the MRC, the UK Engineering and Physical Sciences Research Council, the UK Economic and Social Research Council, the Department of Health and Social Care (England), the Chief Scientist Office of the Scottish Government Health and Social Care Directorates, the Health and Social Care Research and Development Division (Welsh Government), the Public Health Agency (Northern Ireland), the British Heart Foundation, and the Wellcome Trust. SML is an investigator on the European Union Horizon 2020-funded BIOMAP Consortium. CHS acknowledges support for this research from the NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust and the Psoriasis Association. CWL is funded by a UKRI Future Leaders Fellowship. LAT is funded by UKRI, the NIHR, and the MRC. The views expressed are those of the authors and not necessarily those of the NIHR, ICNARC, NHS England, Public Health England, or the UK Department of Health and Social Care. We are very grateful for all the support received from the TPP Technical Operations team throughout this work, and for generous assistance from the information governance and database teams at NHS England and NHSX. Additionally, the North East Commissioning Support Unit provided support on behalf of all Commissioning Support Unit to aggregate the high-cost drugs data. This study uses electronic health records, data are provided by patients and collected by the NHS as part of their care and support. This publication is based on data derived from the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database. The Case Mix Programme is the national, comparative audit of patient outcomes from adult critical care coordinated by ICNARC. We thank all the staff in the critical care units participating in the Case Mix Programme. For more information on the representativeness and quality of these data, please contact ICNARC. We are very grateful to Joe West from the University of Nottingham (UK) and Daniel Prieto-Alhambra from the University of Oxford (UK) for comments on an early version of the protocol.

Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

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