Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts
Dr Angel Ys 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 Jw Evans, Liam Smeeth, Ian J Douglas, Ben Goldacre
Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-219517
Objectives To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. Methods 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.
Results 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. Conclusions 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.
INTRODUCTION COVID-19, caused by the SARS-CoV-2, has been diagnosed in approximately 18 million patients with >690 000 deaths in >200 countries as of 5 August 2020. 1
Key messages
What is already known about this subject? ► There have been concerns that non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of COVID-19 disease. Recent observational studies reported no evidence of a harmful effect of NSAID use on COVID-19 severity among patients with COVID-19. ► However, most studies were of much smaller sample size, not general population based or did not specifically investigate individual NSAIDs (eg, naproxen and ibuprofen). ► In addition, limited clinical data are available to advise patients using long-term NSAID treatment (including people with rheumatoid arthritis and osteoarthritis) whether the treatment should be continued or stopped in the context of COVID-19 pandemic.
What does this study add? ► We identified two study populations (2 463 707 people who ever used NSAIDs in the past 3 years from the general population and 1 708 781 people with rheumatoid arthritis/ osteoarthritis) in England using OpenSAFELY platform. We then grouped them into current users and non-users, respectively, in each study population. ► In both populations, no association between..
Abbreviations: COPD, Chronic obstructive pulmonary disease; DMARDs, Disease-modifying antirheumatic drugs. BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)
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"abstract": "<jats:sec><jats:title>Objectives</jats:title><jats:p>To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>",
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