We shouldn't rush to use an unproven malaria drug to treat the coronavirus - STAT

As the pandemic deepens, physicians face an agonizing decision — to medicate or not to medicate?

Here’s the dilemma: Over the past few weeks, some small studies suggested a decades-old malaria drug called hydroxychloroquine may have the potential to combat the novel coronavirus known as Covid-19. And as the results trickled out, the tablet has become more valuable than gold.

Prescriptions and hospital orders jumped, causing shortages. State pharmacy boards, in fact, claimed some doctors were hoarding the medicine for themselves. President Trump touted the tablet by saying he had a “feeling” it would work. The widely watched conservative TV host Laura Ingraham tweeted that one seriously ill patient recovered like “Lazarus” after being given hydroxychloroquine.

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At the urging of the White House, several manufacturers revived production and will donate millions of pills. And now, the Food and Drug Administration has granted emergency use by hospitals.

However, there’s an issue: No one knows if hydroxychloroquine is truly effective against Covid-19 because we don’t have results from full-blown clinical trials.

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For this reason, doctors should avoid prescribing the tablet, except perhaps to the most severely ill patients.

That is a difficult sentence to write.

As the weeks pass, many more people will be infected, and most likely this includes some who are reading this column. And despite conventional wisdom that only the most vulnerable among us might succumb, this is not necessarily true. Just read the obituaries.

Yet the little study data that is available does not offer any assurances hydroxychloroquine can help, or if it does, who might benefit most.

“Some clinicians say it has promise. Okay, fine. Study it, and try to enroll a lot of patients, but let’s not convince patients they’ll get a benefit or so riled up they want to get it no matter what when we don’t know if they’ll get better,” says Holly Fernandez Lynch, an assistant professor of medical ethics at the Perelman School of Medicine at the University of Pennsylvania.

There are studies underway, actually, at the University of Minnesota and Columbia University. And New York state will “fast track” a trial that looks at hydroxychloroquine and an antibiotic called azithromycin.

Meanwhile, too many people are clinging to findings that could hardly be called rigorous.

Earlier this month, a small French study of 42 patients seemed to show hydroxychloroquine, especially when combined with azithromycin, helped decrease patient levels of the virus. But there were issues with the study design — it was not randomized and it lacked information about patients that would have yielded potentially useful comparative data.

The same authors published an update late last week of 80 patients and wrote the same combination of drugs allowed patients to “rapidly discharge from highly contagious wards” after a stay of five days. But there were problems here, too. This was an observational study without any comparative arm. Moreover, these patients had only a mild form of the virus.

A paper published earlier this month in Nature found that hydroxychloroquine limited the ability of Covid-19 to enter cells in laboratory tests, but this is not the same thing as testing in people. Although the researchers maintained the drug has a “good potential” to combat the disease, they acknowledged the “possibility awaits confirmation by clinical trials.”

Another study of 30 patients published last week by researchers in Shanghai reported disappointing results. CT scans showed there was little difference in the progression of the disease among those given hydroxychloroquine and patients who received the standard of care. One of the authors of the Shanghai study told STAT that hydroxychloroquine is not a “magic drug.”

“As physicians, we’re used to basing our decision on data that’s objective, credible, and clinically driven, but the data on the drug is barely there,” said Lewis Nelson, who chairs the Department of Emergency Medicine at Rutgers New Jersey Medical School and University Hospital in Newark. “Reduced viral loads don’t necessarily equate with improved outcomes or reduced transmissibility.”

There are other issues to be concerned about.

For one, hydroxychloroquine may have been safely prescribed for decades, but it is not benign — the drug can cause irregular heart rhythms. Given the mortality risk, the American College of Cardiology suggests any patient prescribed the drug should be part of a clinical trial, while conceding the benefit may outweigh the risk in Covid-19 patients who are in intensive care units or over 70 years old.

Another problem: The rush to prescribe is making it hard for people with lupus and rheumatoid arthritis to get refills, since the drug was approved to treat those illnesses, as well. Presumably, manufacturer donations to the Strategic National Stockpile will alleviate this concern, but there’s no guarantee if many prescriptions are written for people with mild to moderate symptoms.

This possibility may only have been heightened by the emergency use granted by the FDA, which makes the medication available to hospital patients if a clinical trial is not underway. But this could give the wrong impression about the spotty trial data, which the FDA acknowledged was anecdotal. And as Fernandez Lynch points out, it could be easy for some people to confuse the move with an actual FDA approval.

For now, I think the approach taken by such physicians as David Hill makes the most sense.

A pulmonologist in Waterbury, Conn., where he chairs the pharmacy and therapeutic committee at a local hospital, he explained there are protocols for using the drug in patients who are deteriorating and actively looking to participate in clinical trials. Although he says when previously healthy patients are dying, “it does pressure us to just try something, but that is potentially dangerous.”

“My biggest fear is the public will think there is an effective treatment and abandon the physical distancing that is needed to control this epidemic.”

David Hill, pulmonologist

“There is definitely the balance between using unproven therapy and trying to prevent death,” he wrote me. “My biggest fear is the public will think there is an effective treatment and abandon the physical distancing that is needed to control this epidemic. We are using (hydroxychloroquine and a related drug called chloroquine) with reluctance because they may be ineffective or harmful and with the hope that they may work.

“The bottom line is good quality data is desperately needed and poor quality studies or data should not be needlessly hyped.”

Indeed, this may be the medical quagmire of our time.

In the coming weeks, countless people will become infected with a severe case of Covid-19. For some, hydroxochloroquine may be their only hope.

Even so, let’s not work ourselves into a different kind of fever over a medicine that, for the moment, lacks sufficient evidence.