TY - JOUR
AU - Rentsch, Christopher T.
AU - DeVito, Nicholas J.
AU - Mackenna, Brian
AU - Morton, Caroline E.
AU - Bhaskaran, Krishnan
AU - Brown, Jeremy P.
AU - Schultze, Anna
AU - Hulme, William
AU - Croker, Richard
AU - Walker, Alex J.
AU - Williamson, Elizabeth J.
AU - Bates, Chris J.
AU - Bacon, Sebastian C.J.
AU - Mehrkar, Amir
AU - Curtis, Helen J.
AU - Evans, David
AU - Wing, Kevin
AU - Inglesby, Peter
AU - Mathur, Rohini
AU - Drysdale, Henry
AU - Wong, Angel Y.S.
AU - McDonald, Helen I.
AU - Cockburn, Jonathan
AU - Forbes, Harriet
AU - Parry, John
AU - Hester, Frank
AU - Harper, Sam
AU - Smeeth, Liam
AU - Douglas, Ian J.
AU - Dixon, William G.
AU - Evans, Stephen J.W.
AU - Tomlinson, Laurie
AU - Goldacre, Ben
PY - 2020
DA - November
TI - 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
JO - The Lancet Rheumatology
EP - E27
VL - 3
IS - 1
DO - https://doi.org/10.1016/S2665-9913(20)30378-7
AB - 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 non-COVID-19 mortality. 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.
PB - Elsevier
UR - https://www.research.ed.ac.uk/en/publications/45a27c1f-95b1-4657-9f40-8ca558e01b11
KW - Coronavirus (COVID-19)
ER