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0 0.5 1 1.5 2+ Mortality -3% Improvement Relative Risk HCQ for COVID-19  Rentsch et al.  Prophylaxis Is pre-exposure prophylaxis with HCQ beneficial for COVID-19? Retrospective 194,637 patients in the United Kingdom No significant difference in mortality Rentsch et al., The Lancet Rheumatology, Sep 2020 Favors HCQ Favors control

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., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30378-7 (date from preprint)
Sep 2020  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now known with p < 0.00000000001 from 421 studies, recognized in 42 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,800+ studies for 60+ treatments.
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 analysis: 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.
This PaperHCQAll
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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Boulware, Pullen, Bangdiwala, A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid19, N Engl J Med
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