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
Rentsch et al.
, Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in..
, The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30378-7 (date from earlier preprint)
Observational database study of RA/SLE patients in the UK, 194,637 RA/SLE patients with 30,569 having >= 2 HCQ prescriptions in the prior 6 months, HCQ HR 1.03 [0.80-1.33] (HR 0.78 before adjustments).
70 patients with HCQ prescriptions died. One major problem is that there is no knowlege of medication adherence for these 70 - for example, it is possible that they were part of the expected percentage of patients that did not take the medication as prescribed, invalidating the result. Other limitations include confounding by use of bDMARDs and confounding by severity of rheumatological disease.
This study is excluded in the after exclusion results of meta
not fully adjusting for the baseline risk differences within systemic autoimmune patients; medication adherence unknown and may significantly change results.
risk of death, 3.0% higher, HR 1.03, p = 0.83, treatment 70 of 30,569 (0.2%), control 477 of 164,068 (0.3%), adjusted per study.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Rentsch et al., 9 Sep 2020, retrospective, population-based cohort, database analysis, United Kingdom, peer-reviewed, 34 authors.
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
Christopher T Rentsch*, Nicholas J DeVito*, Brian MacKenna*, Caroline E Morton*, Krishnan Bhaskaran, Jeremy P Brown, 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, Ian J Douglas, William G Dixon, Stephen J W Evans, Laurie Tomlinson†, Ben Goldacre†
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.
Findings Between Sept 1, 2019, and March 1, 2020, of 194 637 people with rheumatoid arthritis or systemic lupus
erythematosus, 30 569 (15·7%) received two or more prescriptions of hydroxychloroquine. Between March 1 and
July 13, 2020, there were 547 COVID-19 deaths, 70 among hydroxychloroquine users. Estimated standardised
cumulative COVID-19 mortality was 0·23% (95% CI 0·18 to 0·29) among users and 0·22% (0·20 to 0·25) among
non-users; an absolute difference of 0·008% (–0·051 to 0·066). After accounting for age, sex, ethnicity, use of other
immunosuppressive drugs, and geographical region, no association with COVID-19 mortality was observed (HR 1·03,
95% CI 0·80 to 1·33). We found no evidence of interactions with age or other immunosuppressive drugs. Quantitative
bias analyses indicated that our observed associations were robust to missing information for additional biologic
treatments for rheumatological disease. We observed similar associations with the negative control outcome of
Interpretation We found no evidence of a difference in COVID-19 mortality among people who received
hydroxychloroquine for treatment of rheumatological disease before the COVID-19 outbreak in England. Therefore,
completion of randomised trials investigating pre-exposure prophylactic use of hydroxychloroquine for prevention of
severe outcomes from COVID-19 are warranted.
Funding Medical Research Council.
Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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