Pre-Exposure to Hydroxychloroquine May Not Prevent COVID-19 Mortality in Patients With Rheumatologic Disease

hydroxychloroquine tablets, COVID-19
Researchers evaluated the effectiveness of hydroxychloroquine for the prevention of COVID-19 mortality in patients with rheumatologic disease.

Treatment of rheumatologic disease with hydroxychloroquine (HCQ) was not associated with reduced mortality before the coronavirus disease 2019 (COVID-19) outbreak in England, according to the results of an observational study published in the Lancet.

Studies have shown HCQ to inhibit the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into epithelial cells in vitro, but the effectiveness of HCQ in the prevention of COVID-19 mortality has not yet been determined.

To evaluate whether ongoing routine HCQ use is effective in the prevention of SARS-CoV-2 infection, data were analyzed from 194,637 patients (71.1% women) diagnosed with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Of these patients, 30,569 (15.7%) received 2 or more prescriptions of HCQ in the 6 months before the index date (March 1, 2020). The median age of patients was 66 years (interquartile range, 54-75 years). The primary outcome of the study was COVID-19 mortality, as determined on the death certificate.

During the study period, there were 547 COVID-19 deaths among patients with RA or SLE, 70 of whom were regularly receiving HCQ. The absolute cumulative difference in risk for COVID-19 mortality between users and nonusers was 0.008% (95% CI, -0.051% to 0.066%). Even after adjusting for age, sex, and all other covariates, no significant difference was observed (hazard ratio, 1.08; 95% CI, 0.84-1.40).

Study results showed no evidence that HCQ affected the risk for COVID-19 mortality, a finding that is in contrast to what has been previously hypothesized and may be useful to inform the decision-making of regulatory bodies.

Study limitations included its observational design, the lack of data regarding the use of biologics and disease severity, and the inability to determine whether patients actually took their medications.

Researchers concluded, “…completion of [randomized] trials investigating pre-exposure prophylactic use of [HCQ] for prevention of severe outcomes from COVID-19 are warranted.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Rentsch CT, DeVito NJ, MacKenna B, et al. 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. Lancet. Published online November 5, 2020. doi:10.1016/S2665-9913(20)30378-7