Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study

Abstract

Background Hydroxychloroquine is one of several agents being evaluated in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to examine whether patients with rheumatological conditions receiving chronic hydroxychloroquine therapy are at less risk of developing SARS-CoV-2 infection than those not receiving hydroxychloroquine. Methods This retrospective cohort study included de-identified information of all veterans in the US Veterans Health Administration clinical administrative database aged 18 years or older with rheumatoid arthritis, systemic lupus erythematosus, or associated rheumatological conditions (based on International Classification of Diseases, 10th edition, diagnostic codes) who were alive on March 1, 2020. A propensity score was calculated for each patient, and each patient who was receiving hydroxychloroquine was matched to two patients who were not receiving hydroxychloroquine (controls). The primary endpoint was the proportion of patients with PCR-confirmed SARS-CoV-2 infection among those receiving chronic hydroxychloroquine versus the propensity-matched patients not receiving chronic hydroxychloroquine between March 1 and June 30, 2020. Secondary outcomes were hospital admission associated with SARS-CoV-2 infection; intensive care requirement associated with SARS-CoV-2 infection; mortality associated with SARS-CoV-2 infection; and overall rates of any hospital admission and mortality (ie, all cause). Multivariate logistic regression analysis was done to determine independent variables for the development of active SARS-CoV-2 infection. Findings Between March 1 and June 30, 2020, 10 703 patients receiving hydroxychloroquine and 21 406 patients not receiving hydroxychloroquine were included in the primary analysis. The incidence of active SARS-CoV-2 infections during the study period did not differ between patients receiving hydroxychloroquine and patients not receiving hydroxychloroquine (31 [0·3%] of 10 703 vs 78 [0·4%] of 21 406; odds ratio 0·79, 95% CI 0·52–1·20, p=0·27). There were no significant differences in secondary outcomes between the two groups in patients who developed active SARS-CoV-2 infection. For all patients in the study, overall mortality was lower in the hydroxychloroquine group than in the group of patients who did not receive hydroxychloroquine (odds ratio 0·70, 95% CI 0·55–0·89, p=0·0031). In multivariate logistic regression analysis, receipt of hydroxychloroquine was not associated with the development of active SARS-CoV-2 infection (odds ratio 0·79, 95% CI 0·51–1·42). Interpretation Hydroxychloroquine was not associated with a preventive effect against SARS-CoV-2 infection in a large group of patients with rheumatological conditions. Funding None.

The contribution of the observational research design to COVID-19 research

“…In multivariate logistic regression analyses, hydroxychloroquine use was not independently associated with SARS-CoV-2 infection risk. The results from this male-predominant population of veterans with rheumatic disease are similar to those reported by the COVID-19 Global Rheumatology Alliance 6 , 7 and in the general population within the setting of an RCT. 5 …”

“…In The Lancet Rheumatology , Chris Gentry and colleagues 7 leveraged a large dataset derived from the electronic health record of the US Veterans Health Administration (VHA) to carry out a retrospective, observational, propensity-matched analysis comparing the rate of laboratory-confirmed COVID-19 in adults with rheumatic diseases prescribed hydroxychloroquine with patients treated with other rheumatic disease medications. From 70 270 patients with an International Classification of Diseases (10th revision; ICD-10) diagnosis of rheumatic disease, the authors compared 10 703 patients treated with hydroxychloroquine who demonstrated satisfactory hydroxychloroquine adherence to 21 406 patients not treated with hydroxychloroquine.…”

COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease

“…187 Several other groups have also suggested the lack of benefit of HCQ against contracting or developing severe COVID-19 in patients with SLE and other rheumatic diseases. [188][189][190][191][192][193][194] A retrospective study from Spain included patients with several different rheumatic or autoimmune diseases, nine of which had SLE. They found no statistically significant between-group differences for rheumatologic diagnosis or baseline use of immunosuppressive therapy except for sGC use, which was more frequent in hospitalized patients.…”

“…233,234 Multiple recent studies, including observational data from patients with immune-mediated diseases on long-term D 1 8 3 X XHCQ as well as large randomized clinical trials, have consistently demonstrated the lack of efficacy of HCQ in preventing the viral infection or improving any COVID-19-related outcomes. 171,190,[235][236][237][238] However, for several weeks after the preclinical studies and limited observational data came to light, HCQ shortages ensued in many countries as its use was redirected toward prophylaxis or management of COVID-19, leading to inadequate supplies of the drug for many patients with SLE worldwide. 239,240 For instance, an electronic survey distributed to the SD 1 8 4 X XLE International Collaborating Clinics D 1 8 5 X Xmembers with SLE-affiliated centers aimed to evaluate physicians' experiences with D 1 8 6 X XHCQ shortages during the pandemic.…”

<p>Flattening the Risk: Pre-Exposure Prophylaxis for COVID-19</p>

“…45 In a retrospective cohort study of 32,109 rheumatic disease patients from the US Veterans Health Administration, the incidence of SARS-CoV-2 infection was equivalent regardless of chronic HCQ use (0.3% in users versus 0.4% in non-users), but mortality was significantly decreased in patients taking HCQ (odds ratio 0.70, p=0.0031). 46 HCQ PrEP failed to prevent experimental viral infection in Syrian hamsters and macaque monkeys, but all of the animals cleared their infections and none died. Thus, the hamster and monkey PrEP models have questionable significance for humans.…”