THE SCIENCE OF HYDROXY

Brian Owens – THE LANCET April 01, 2020

Excitement around hydroxychloroquine for treating COVID-19 causes challenges for rheumatology

Excitement about a potential new treatment for the coronavirus disease 2019 (COVID-19) pandemic currently engulfing the world is causing problems for patients with arthritis and systemic lupus erythematosus (SLE), who routinely use the drug to control their symptoms. The antimalarial drug chloroquine and its safer derivative hydroxychloroquine have been used since the 1940s to treat autoimmune disorders, says Thomas Dörner, a rheumatologist at the Charité University Hospital in Berlin. Though the drug is rarely used for rheumatoid arthritis, around two-thirds of patients with SLE in Europe use hydroxychloroquine to manage their symptoms, and it is the only known therapy so far for primary Sjögren’s syndrome, he says. But the drug has also attracted attention over the past few decades as a potential antiviral agent, currently as a possible treatment for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19. Reports from China found that chloroquine could inhibit SARS-CoV-2 in vitro, and showed apparent efficacy in treating COVID-19 in humans. A small non-randomised trial in France also found hydroxychloroquine to be a promising potential treatment. The findings have prompted many, including US President Donald Trump, to tout hydroxychloroquine as a game-changer in the fight against COVID-19. The US Food and Drug Administration has designated hydroxychloroquine for off-label, compassionate use for treating COVID-19, and WHO added the drug to its large global SOLIDARITY trial to test a variety of potential treatments. But virologists and infectious disease experts caution that the excitement is premature. “Whether hydroxychloroquine works in vivo is not proven for any virus, and in fact in randomised controlled trials against a number of viruses, including influenza, it doesn’t work at all,” says Douglas Richman, a virologist and infectious disease physician at the University of California, San Diego. “It’s my personal prejudice that this is also going to be the case with coronavirus.” Hydroxychloroquine has been studied as a possible antiviral for approximately the past 40 years, says Richman.

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