Hydroxychloroquine fails to prevent COVID-19 in patients with lupus
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Patients with systemic lupus erythematosus who received hydroxychloroquine were just as likely to develop severe COVID-19 as those who were not treated with antimalarials, according to data from the COVID-19 Global Rheumatology Alliance registry.
“The use of hydroxychloroquine (HCQ) in the prophylaxis and treatment of coronavirus disease 2019 (COVID-19) has received significant attention by politicians and media figures,” Maximilian F. Konig, MD, of the Johns Hopkins University School of Medicine, and colleagues wrote in a letter published in Annals of the Rheumatic Diseases. “This has occurred despite limited data supporting its efficacy in COVID-19 as well as considerable concern about its safety when used at high doses (>400mg daily) and in combination with other QT interval prolonging drugs.”
“An inaccurate narrative has emerged in recent weeks that patients with systemic lupus erythematosus (SLE) who are taking HCQ as a baseline therapy are less affected by or do not develop COVID-19,” they added. “This assumption has been challenged by Monti and Montecucco, referencing data from the COVID-19 Global Rheumatology Alliance registry on patients with rheumatic disease that previously identified 19/110 (17%) patients with SLE.”
To analyze antimalarials as prophylaxis for COVID-19, Konig and colleagues analyzed data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Using the data available as of April 17, the researchers identified 80 patients with SLE and COVID-19.
Among these patients, 90% were women and 86% were younger than 65 years. Further, 64% of patients with SLE were receiving either hydroxychloroquine or chloroquine — 30% as monotherapy — prior to developing COVID-19.
According to the researchers, treatment with antimalarials had no impact on whether patients with SLE required the maximum level of care related to COVID-19, including noninvasive and invasive ventilation or extracorporeal membrane oxygenation.
The researchers also noted that, at the time of their analysis, 21.1% of the 573 total reported patients with rheumatic disease in the registry were treated with an antimalarial prior to COVID-19 onset. Despite this, 49.6% still required hospitalization.
“In patients with lupus, escalation to maximum level of care (non-invasive ventilation, invasive ventilation or extracorporeal membrane oxygenation [ECMO]) was required regardless of HCQ use,” Konig and colleagues wrote. “Thus, patients with lupus — even if they are using an antimalarial such as HCQ as baseline therapy — can develop SARS-CoV-2 infection and severe COVID-19 at similar frequency as lupus patients not on antimalarials.”
Perspective
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Robin K. Dore, MD
There has been much written and said about the use of hydroxychloroquine in treating patients with COVID-19. Initially, it was reported that patients with lupus taking HCQ were protected against developing a COVID-19 infection but data from the COVID-19 Global Rheumatology Alliance does not support this concept.
As of April 17, 2020, 80 patients with COVID-19 and lupus were identified 64% (51/80) were taking anti-malarial therapy. In this registry, 21.1% (121/573) of all reported patients were treated with an anti-malarial prior to developing COVID-19 and 49.6% (60/121) required hospitalization. In patients with lupus, frequency of hospitalization did not differ between patients treated with anti-malarial therapy vs. non-users.
In vitro studies have indicated activity of antimalarial therapy against SARS-COV-2 and MERS-CoV but in vitro potency cannot be expected to translate into in vivo efficacy. It is uncertain as to what drug concentrations need to be achieved and in which tissue: whole blood vs. lung parenchyma vs. epithelial lining fluid. Without an understanding of the known HCQ concentrations and in what tissue, therapeutic doses that are effective are difficult to predict.
The usual doses of HCQ used to treat rheumatic diseases do not reach the EC090 for SARS-CoV-2. In a mouse model, the lung concentrations were higher than the blood levels but it is uncertain if this is the case in humans. In an open-label, randomized, controlled trial using an HCQ dose up to 1200 mg for 3 days and a maintenance dose of 800 mg per day for 2-3 weeks, there was no suppression of viral replication. Thus, for anti-malarial therapy to be effective in preventing COVID-19 infection in lupus patients, much higher doses might need to be used that can be associated with intolerance and reported cardiac toxicity.
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