Cross-sectional case-control studies (Blue)
In this article the authors aimed to evaluate the effectiveness of hydroxychloroquine for prevention of COVID-19 mortality, as opposed to treatment for the disease. They performed 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. All adults aged 18 years and older registered with a general practice for 1 year or more on March 1, 2020 were included. Cox regression were applied 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. 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). The authors found no evidence of interactions with age or other immunosuppressive drugs. Quantitative bias analyses indicated that their observed associations were robust to missing information for additional biological treatments for rheumatological disease. Moreover, they observed similar associations with the negative control outcome of non-COVID-19 mortality. The authors concluded that they 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.