Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: An OpenSAFELY cohort analysis based on two cohorts

Angel Y.S. Wong; Brian MacKenna; Caroline E. Morton; Anna Schultze; Alex J. Walker; Krishnan Bhaskaran; Jeremy P. Brown; Christopher T. Rentsch; Elizabeth Williamson; Henry Drysdale; Richard Croker; Seb Bacon; William Hulme; Chris Bates; Helen J. Curtis; Amir Mehrkar; David Evans; Peter Inglesby; Jonathan Cockburn; Helen I. McDonald; Laurie Tomlinson; Rohini Mathur; Kevin Wing; Harriet Forbes; Rosalind M. Eggo; John Parry; Frank Hester; Sam Harper; Stephen J.W. Evans; Liam Smeeth; Ian J. Douglas; Ben Goldacre

doi:10.1136/annrheumdis-2020-219517

Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: An OpenSAFELY cohort analysis based on two cohorts

Angel Y.S. Wong, Brian MacKenna, Caroline E. Morton, Anna Schultze, Alex J. Walker, Krishnan Bhaskaran, Jeremy P. Brown, Christopher T. Rentsch, Elizabeth Williamson, Henry Drysdale, Richard Croker, Seb Bacon, William Hulme, Chris Bates, Helen J. Curtis, Amir Mehrkar, David Evans, Peter Inglesby, Jonathan Cockburn, Helen I. McDonaldLaurie Tomlinson, Rohini Mathur, Kevin Wing, Harriet Forbes, Rosalind M. Eggo, John Parry, Frank Hester, Sam Harper, Stephen J.W. Evans, Liam Smeeth, Ian J. Douglas, Ben Goldacre

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Abstract

To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. We conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region. In study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use. We found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.

Original language	English
Pages (from-to)	943-951
Number of pages	9
Journal	Annals of the Rheumatic Diseases
Volume	80
Issue number	7
Early online date	21 Jan 2021
DOIs	https://doi.org/10.1136/annrheumdis-2020-219517
Publication status	Published - 17 Jun 2021
Externally published	Yes

Bibliographical note

Funding Information:
Competing interests BG has received research funding from Health Data

Funding Information:
Funding TPP provided technical expertise and infrastructure within their data centre pro bono in the context of a national emergency. BG’s work on better use of data in healthcare more broadly is currently funded in part by: National Institute for Health Research (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 Wellcome, MRC, NIHR, UKRI, British Council, GlaxoSmithKline, British Heart Foundation, and Diabetes UK outside this work. AYSW holds a fellowship from British Heart Foundation. JPB is funded by a studentship from GlaxoSmithKline. AS is employed by London School of Hygiene and Tropical Medicine on a fellowship sponsored by GlaxoSmithKline. KB holds a Sir Henry Dale fellowship jointly funded by Wellcome and the Royal Society (107731/Z/15/Z)). HIM is funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Immunisation, a partnership between Public Health England and London School of Hygiene and Tropical Medicine. RM holds a Sir Henry Wellcome fellowship (201375/Z/16/Z)). EW holds grants from MRC. RG holds grants from NIHR and MRC. ID holds grants from NIHR and GlaxoSmithKline. HF holds a UKRI fellowship.

Publisher Copyright:
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Keywords

arthritis
COVID-19
epidemiology
osteoarthritis
rheumatoid

ASJC Scopus subject areas

Rheumatology
Immunology and Allergy
Immunology
General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1136/annrheumdis-2020-219517Licence: CC BY

Cite this

Wong, A. Y. S., MacKenna, B., Morton, C. E., Schultze, A., Walker, A. J., Bhaskaran, K., Brown, J. P., Rentsch, C. T., Williamson, E., Drysdale, H., Croker, R., Bacon, S., Hulme, W., Bates, C., Curtis, H. J., Mehrkar, A., Evans, D., Inglesby, P., Cockburn, J., ... Goldacre, B. (2021). Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: An OpenSAFELY cohort analysis based on two cohorts. Annals of the Rheumatic Diseases, 80(7), 943-951. https://doi.org/10.1136/annrheumdis-2020-219517

Wong, AYS, MacKenna, B, Morton, CE, Schultze, A, Walker, AJ, Bhaskaran, K, Brown, JP, Rentsch, CT, Williamson, E, Drysdale, H, Croker, R, Bacon, S, Hulme, W, Bates, C, Curtis, HJ, Mehrkar, A, Evans, D, Inglesby, P, Cockburn, J, McDonald, HI, Tomlinson, L, Mathur, R, Wing, K, Forbes, H, Eggo, RM, Parry, J, Hester, F, Harper, S, Evans, SJW, Smeeth, L, Douglas, IJ & Goldacre, B 2021, 'Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: An OpenSAFELY cohort analysis based on two cohorts', Annals of the Rheumatic Diseases, vol. 80, no. 7, pp. 943-951. https://doi.org/10.1136/annrheumdis-2020-219517

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title = "Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: An OpenSAFELY cohort analysis based on two cohorts",

abstract = "To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. We conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region. In study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use. We found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.",

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author = "Wong, {Angel Y.S.} and Brian MacKenna and Morton, {Caroline E.} and Anna Schultze and Walker, {Alex J.} and Krishnan Bhaskaran and Brown, {Jeremy P.} and Rentsch, {Christopher T.} and Elizabeth Williamson and Henry Drysdale and Richard Croker and Seb Bacon and William Hulme and Chris Bates and Curtis, {Helen J.} and Amir Mehrkar and David Evans and Peter Inglesby and Jonathan Cockburn and McDonald, {Helen I.} and Laurie Tomlinson and Rohini Mathur and Kevin Wing and Harriet Forbes and Eggo, {Rosalind M.} and John Parry and Frank Hester and Sam Harper and Evans, {Stephen J.W.} and Liam Smeeth and Douglas, {Ian J.} and Ben Goldacre",

note = "Funding Information: Competing interests BG has received research funding from Health Data Funding Information: Funding TPP provided technical expertise and infrastructure within their data centre pro bono in the context of a national emergency. BG{\textquoteright}s work on better use of data in healthcare more broadly is currently funded in part by: National Institute for Health Research (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{\textquoteright}s grants on this work. LS reports grants from Wellcome, MRC, NIHR, UKRI, British Council, GlaxoSmithKline, British Heart Foundation, and Diabetes UK outside this work. AYSW holds a fellowship from British Heart Foundation. JPB is funded by a studentship from GlaxoSmithKline. AS is employed by London School of Hygiene and Tropical Medicine on a fellowship sponsored by GlaxoSmithKline. KB holds a Sir Henry Dale fellowship jointly funded by Wellcome and the Royal Society (107731/Z/15/Z)). HIM is funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Immunisation, a partnership between Public Health England and London School of Hygiene and Tropical Medicine. RM holds a Sir Henry Wellcome fellowship (201375/Z/16/Z)). EW holds grants from MRC. RG holds grants from NIHR and MRC. ID holds grants from NIHR and GlaxoSmithKline. HF holds a UKRI fellowship. Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.",

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doi = "10.1136/annrheumdis-2020-219517",

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AU - Walker, Alex J.

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AU - Brown, Jeremy P.

AU - Rentsch, Christopher T.

AU - Williamson, Elizabeth

AU - Drysdale, Henry

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AU - Wing, Kevin

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AU - Eggo, Rosalind M.

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N1 - Funding Information: Competing interests BG has received research funding from Health Data Funding Information: Funding TPP provided technical expertise and infrastructure within their data centre pro bono in the context of a national emergency. BG’s work on better use of data in healthcare more broadly is currently funded in part by: National Institute for Health Research (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 Wellcome, MRC, NIHR, UKRI, British Council, GlaxoSmithKline, British Heart Foundation, and Diabetes UK outside this work. AYSW holds a fellowship from British Heart Foundation. JPB is funded by a studentship from GlaxoSmithKline. AS is employed by London School of Hygiene and Tropical Medicine on a fellowship sponsored by GlaxoSmithKline. KB holds a Sir Henry Dale fellowship jointly funded by Wellcome and the Royal Society (107731/Z/15/Z)). HIM is funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Immunisation, a partnership between Public Health England and London School of Hygiene and Tropical Medicine. RM holds a Sir Henry Wellcome fellowship (201375/Z/16/Z)). EW holds grants from MRC. RG holds grants from NIHR and MRC. ID holds grants from NIHR and GlaxoSmithKline. HF holds a UKRI fellowship. Publisher Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

PY - 2021/6/17

Y1 - 2021/6/17

N2 - To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. We conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region. In study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use. We found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.

AB - To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. We conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region. In study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use. We found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.

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Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: An OpenSAFELY cohort analysis based on two cohorts

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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