The hype surrounding hydroxychloroquine (HCQ) as a potential treatment for COVID-19 has led to problems for patients who use the drug to treat conditions like lupus, leading to shortages in pharmacies and worries about potentially dangerous side-effects, according to rheumatologists.
Following preliminary reports in March that the antimalarial drug could be effective in treating COVID-19—and a strong endorsement from US President Donald Trump—prescriptions of the drug spiked. In the USA, for example, prescriptions increased by more than 2000% in the 10-week period between Feb 16 and April 25 this year, compared with the same period last year.
Similar increases in HCQ prescriptions in Europe led to temporary shortages of the drug for rheumatology patients, says Nathalie Costedoat-Chalumeau, a rheumatologist at Cochin Hospital in Paris, France. “We had issues with delivering treatment, our patients couldn't find it in the pharmacy,” she says, although the problem has now been mostly resolved. Thomas Dörner, a rheumatologist at the Charité University Hospital in Berlin, says that in Germany, rheumatology patients were given preferential access to HCQ, which ensured shortages were short-lived.
A bigger problem is that the extensive news coverage of the side-effects of HCQ has left some rheumatology patients worried about the safety of a drug that they take every day. Multiple studies on the use of HCQ in patients with COVID-19 have highlighted the risk of cardiac complications for those using the drug, especially when taken in combination with the antibiotic azithromycin. The drug combination has been linked to an abnormal heart rhythm, in the form of a prolonged QT interval, in small observational studies in France and the USA. In addition one observational study of more than 1400 COVID-19 patients in New York City-area hospitals found that those who were given HCQ and azithromycin were more than twice as likely to suffer a heart attack as those who were not.
The first randomised controlled clinical trial of HCQ found no serious side-effects, but that was to be expected given that the participants were relatively young and healthy, and the study excluded people with pre-existing cardiac issues, says David Boulware, an infectious disease physician at the University of Minnesota in Minneapolis (MN, USA) who led the study. More importantly, the study showed that the drug was ineffective as a post-exposure prophylactic for COVID-19.
These concerns over safety, and a lack of evidence of any benefit, have led the US National Institutes of Health, the US Food and Drug Administration, and the American College of Physicians to recommend against use of HCQ to treat COVID-19 unless it is part of a clinical trial.
“The evidence is really insufficient that it helps, and in many cases it seems to hurt,” says Jacqueline Fincher, president of the American College of Physicians. “Continuing clinical trials will help to strengthen the evidence of whether the drug works or not, and ensure that anyone taking it is being properly monitored for the risks,” she says.
One study, published in The Lancet, that found an increased risk of death among COVID-19 patients treated with HCQ prompted WHO to temporarily suspend the HCQ arm of its global SOLIDARITY clinical trial. But the veracity of the data in that study was widely questioned and heavily criticised, and the article has since been retracted.
All the attention on the potential cardiac side-effects now has rheumatology patients wondering if it is safe to continue using the drug. “The heart issue is a new one. We never discussed it with patients because it was so rare, but what they have been seeing on social media is crazy,” says Costedoat-Chalumeau. “I start all my appointments talking about it now.”
Dörner and Costedoat-Chalumeau both say the risk to rheumatology patients is very low. The dose used in patients with COVID-19 is much higher, double or even triple what is given to those with lupus, and COVID-19 is itself associated with cardiac complications, which the drug could exacerbate. “This is something that may be specific to COVID-19 and the higher doses,” says Costedoat-Chalumeau.
David Holtgrave, dean of public health at the State University of New York at Albany (Albany, NY, USA) who worked on the study that found a link with heart attacks, agrees that the cardiac risks seen in patients with COVID-19 should not be extrapolated to other patients. “Our patients were hospitalised, and many were quite ill,” he says. “It's very different than using these drugs for other conditions.”
Boulware says it is too early to completely cast aside HCQ for COVID-19—he has two more trials underway looking at pre-exposure prophylaxis and early treatment—but he also says the results are not looking very promising. Many researchers and physicians now feel it is time to move on to other ideas.
“It was not a bad idea to try, but now all the evidence is against using it to treat this condition,” says Costedoat-Chalumeau.
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