Hydroxychlorqine for COVID-19: Time To Move On?

Hydroxychloroquine has become a part of the COVID story that will not go away. 

And with another research study reported today in JAMA showing no benefit of the drug in hospitalized patients with COVID-19, the journal asks the fundamental question: Why do we continue to believe this drug has benefit in treating this pandemic illness, and why won’t science prevail?

To which we respond: Why are we surprised????

The study, performed by a clinical trial collaborative under the guidance of the National Heart and Lung Institute of the National Institutes of Health included 479 patients in 34 hospitals around the country who had the presumed or confirmed diagnosis of COVID-19. Half received hydroxychloroquine, half a placebo. 

The results are clear cut: a number of factors were evaluated, including ethnicity, and in no circumstance did the use of hydroxychloroquine lead to an improved outcome. Period, end of sentence: no benefit. It didn’t reduce the severity of disease, it didn’t improve outcomes, it didn’t lead to fewer deaths.  In fact, the effect of hydroxychloroquine was so lacking that the study was stopped earlier than planned.

This probably wasn’t a surprising result, given that a number of other trials from around the world treating COVID patients in different circumstances—including studies to find out if hydroxychloroquine prevented people at high risk of exposure from getting COVID-19—all showed the same outcome: no meaningful benefit in preventing COVID-19 or altering the course of the illness. 

An editorial that accompanied today’s research report asked the basic question of why so many studies—all of which have come to the same negative conclusion—were done in the first place?

The answer, in simple terms: desperation.

The editorial refreshes our memories that when COVID first made its appearance on the world stage we knew that it was a serious viral illness that could lead to death. We didn’t know much else, and we certainly didn’t have any therapies that had proven themselves to improve outcomes at that early period of time. So people were scared. And doctors were scared. “Do something!!!” became the mantra heard around the world.

Then, voila, hydroxychloroquine (HCQ) came to the rescue as a possible treatment: there had been previous laboratory studies suggesting that HCQ may impact the ability of the SARS virus to infect cells—in a test tube. A study of a handful of patients appeared online suggesting benefit, notwithstanding the fact that it wasn’t exactly the kind of study experts would rely on for a definitive answer. But it provided a hook—a hook that could mean the difference between life and death.

So it was off to the races: HCQ was widely prescribed and patients who had been taking the drug for diseases where it was known to be effective had trouble getting their supply of the medication from their pharmacies. The President touted its benefit publicly and frequently, and the federal government stockpiled huge amounts of the medicine. We were on a roll. And, in fact, we may still be on the same roll—however that is a topic for another day.

Organizations like the American Medical Association issued pleas that doctors and patients use HCQ sparingly for COVID-19. The Arthritis Foundation issued similar pronouncements. Then the Food and Drug Administration issued what is called an Emergency Use Authorization which gave credibility to the possibility that the drug worked in reducing the impact of COVID. Shortly after, when it was clear that the drug did not improve outcomes, the agency withdrew the authorization. 

Then the more appropriately designed studies started to come in, and it became clear that HCQ did not help patients survive COVID-19. Anecdotes notwithstanding, various clinical trials did not show benefit. 

And that brings us to today’s report and editorial. Another piece of evidence that HCQ doesn’t work to help patients. Yet doctors and consumers continue to believe that it does.

The editorial in JAMA sums up the situation very clearly:

“The clear, unambiguous, and compelling lesson from the hydroxychloroquine story for the medical community and the public is that science and politics do not mix. Science, by definition, requires diligence and an honest assessment of findings; politics not so much. The number of articles in the peer-reviewed literature over the last several months that have consistently and convincingly demonstrated the lack of efficacy of a highly hyped ‘cure’ for COVID-19 represents the consequence of the irresponsible infusion of politics into the world or scientific evidence and discourse. For other potential therapies or interventions for COVID-19 (or any other diseases), this should not happen again.”

But stay tuned, since this is not the end of the story.

This weekend, the American Medical Association’s House of Delegates will convene and consider a resolution supporting the the right of physicians to prescribe HCQ “until sufficient evidence becomes available to conclusively demonstrate that the harm associated with use (of HCQ) outweighs benefit early in the disease course. Implying that such treatment is inappropriate contradicts AMA policy…that addresses off label prescriptions as appropriate in the judgement of the prescribing physician.”

One wonders if the judgment of the JAMA editorial will have any influence as to whether or not there is sufficient evidence to show that HCQ simply does not benefit consumers and patients in preventing infection or altering the course of COVID-19.

Undoubtedly the HCQ story is going to continue, despite the evidence. And the world is about to find out whether the AMA believes in science and evidence, or is mired too deeply in COVID-19 politics. Hopefully, we will see that  in the house of medicine, evidence prevails.