Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform
PhD Christopher T Rentsch, MPH Nicholas J Devito, Brian Mackenna, Caroline E Morton, Prof Krishnan Bhaskaran, PhD Jeremy P Brown, MSc Anna Schultze, William J Hulme, Richard Croker, Alex J Walker, Elizabeth J Williamson, Chris Bates, Seb Bacon, Amir Mehrkar, Helen J Curtis, David Evans, Kevin Wing, Peter Inglesby, Rohini Mathur, Henry Drysdale, Angel Y S Wong, Helen I Mcdonald, Jonathan Cockburn, Harriet Forbes, John Parry, Frank Hester, Sam Harper, Liam Smeeth, PhD Ian J Douglas, William G Dixon, Stephen J W Evans, Laurie Tomlinson, Ben Goldacre
The Lancet Rheumatology, doi:10.1016/s2665-9913(20)30378-7
Background Hydroxychloroquine has been shown to inhibit entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into epithelial cells in vitro, but clinical studies found no evidence of reduced mortality when treating patients with COVID-19. We aimed to evaluate the effectiveness of hydroxychloroquine for prevention of COVID-19 mortality, as opposed to treatment for the disease.
Methods We did a prespecified observational, population-based cohort study using national primary care data and linked death registrations in the OpenSAFELY platform, which covers approximately 40% of the general population in England, UK. We included all adults aged 18 years and older registered with a general practice for 1 year or more on March 1, 2020. We used Cox regression to estimate the association between ongoing routine hydroxychloroquine use before the COVID-19 outbreak in England (considered as March 1, 2020) compared with non-users of hydroxychloroquine and risk of COVID-19 mortality among people with rheumatoid arthritis or systemic lupus erythematosus. Model adjustment was informed by a directed acyclic graph.
A Cumulative mortality (%)
Days since March 1, 2020 No hydroxychloroquine Hydroxychloroquine CEM, CB, SB, AM, HJC, LS, IJD, SW, LT, and BG were responsible for project administration. LS and BG were responsible for resources. BM, CEM, WJH, AJW, CB, SB, DE, PI, JC, FH, and SH were responsible for software. LS, IJD, WGD, SJWE, LT, BG were responsible for supervision. CTR and KB were responsible for visualisation. CTR, NJD, BM, IJD, SJWE, and LT were responsible for writing the first draft of the manuscript. CT, NJD, BM, CEM, KB, JPB, AS, WJH, RC, AJW, EJW, CB, SB, AM, HJC, DE, KW, PI, RM, HD, AYSW, HIM, JC, HF, JP, FH, SH, LS, IJD, WGD, SJWE, LT, and BG were responsible for writing (review and editing). CTR, CEM, AJW, CB, and JC were responsible for verification of the underlying data. CTR, LS, and BG were guarantors.
Declaration of interests BG has received research funding from the Laura and John Arnold Foundation, the National Health Service (NHS) National Institute for Health Research (NIHR), the NIHR School of Primary Care Research, the NIHR Oxford Biomedical Research Centre, the MohnWestlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, the Wellcome Trust, the Good Thinking Foundation, Health Data Research UK, the Health Foundation, and WHO; he also receives personal income from speaking and writing for lay audiences on the misuse of science. IJD reports grants from NIHR, and has received unrestricted research grants and holds shares in..
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