Ivermectin's boom and bust

Stop the presses! Another large clinical trial of the controversial drug ivermectin, published in JAMA Internal Medicine, has found that it did not prevent people with COVID-19 from developing severe disease.
 
In this new study in Malaysia, 480 patients with confirmed COVID-19, hospitalized or confined to a quarantine center, were randomly assigned to take ivermectin or a placebo. The drug turned out to be no better than the placebo not only for stopping the progression of the disease, but also at preventing the need for ventilation, admission to the ICU, or death.

Previous large clinical trials of outpatients with confirmed COVID-19 infections in Argentina and Brazil and of outpatients and hospitalized patients with mild disease in Colombia, involving a total of more than 2,200 patients, produced similarly disappointing results.

With each new well-conducted large trial, the picture becomes clearer that ivermectin is not the “miracle” cure for COVID-19 that some claim it is.

But cold facts are unlikely to put an end to the controversy over this drug in these partisan, politicized times. Evidently, what some people believe depends not on what good studies find, but on where they stand in the political spectrum, who they support politically, and how much they trust or don’t trust FDA, Fox News, Tony Fauci, scientists, YouTube videos, big Pharma, the mainstream media, Facebook groups, Bill Gates, Twitter, or the CDC.

In fact, data published in the same issue of JAMA Internal Medicine showed that right after the first positive (but highly premature) publicity about ivermectin in the United States in December 2020, prescriptions for ivermectin skyrocketed to about three times as high in those counties with a heavy Republican vote in the presidential election the month before, compared with counties that voted most heavily Democratic.

How did ivermectin become so political? It’s an inexpensive, widely available, and generally safe drug used all over the world to successfully treat river blindness and strongyloidiasis in people caused by infections with parasitic worms. Topical versions are FDA-approved to treat lice. So why all the fuss? 

The story begins in April 2020 when Australian scientists combined a very high concentration of ivermectin and the coronavirus in the laboratory (not in people!) and found that the drug stopped the virus from reproducing. Of course, long is the list of drugs for cancer and just about every major disease on the planet that looked promising in the test tube, but flamed out in actual humans. In this particular case, the level of ivermectin tested would likely be toxic to humans.

Nonetheless, the scientists quickly posted their finding online, unfortunately with a misleading title implying that FDA had approved this use of ivermectin: “The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro.”
 
Their post went viral, especially in Central and South America where medical facilities were already overwhelmed with COVID-19 patients and had little to treat them. In contrast, ivermectin was readily available, cheap and came with a good safety record, so physicians started giving the drug to their patients. It was at least something they could do. 

Among ivermectin's biggest boosters was Brazil's president Jair Bolsonaro whose government promoted the treatment of COVID-19 with the use of "COVID kits" containing the drug. (The appeal of repurposing drugs and the pitfalls of doing so were highlighted early in the pandemic in my testimony before the House Science, Space, and Technology's Investigations and Oversight Subcommittee.)

Soon, people were posting “scientific” reports on the Internet about how ivermectin did or did not seem to be speeding recovery or preventing death from COVID-19. These reports, which eventually numbered more than 75, usually involved small numbers of patients or inadequate controls. In normal times, most would not be reliable enough to be published. But for a world desperate for news about what might work against the pandemic, these unvetted reports are posted online for anyone to scour for even the faintest glimmer of hope against COVID-19.

Before long, a few curious scientists began in their spare time to examine these posted studies in detail. What they found was alarming. 

An early influential study from Egypt, for example, claiming that ivermectin reduced COVID deaths by an improbable 90 percent, contained dozens of patient records that appeared to be duplicates, inconsistencies between raw data and information in the paper, patients who had died before the study started, and data that seemed to be too consistent to have occurred by chance. The paper was retracted.

And that’s not all. A study purportedly of 1,408 COVID-19 patients from 169 hospitals on 3 continents was posted online in April 2020 claiming that ivermectin treatment reduced the risk of death. The study was viewed nearly 90,000 times and downloaded more than 15,000 times during its first two months and became part of the rationale for the Peruvian government officially recommending ivermectin for the treatment of COVID-19.

However, after serious questions were raised about the authenticity of the study’s patient database, the researchers, including one from Harvard Medical School and another from the University of Utah, retracted the study. Peru followed by retracting its advice to take ivermectin.

And in a study of 50 patients from Lebanon that claimed ivermectin treatment reduced hospital admissions, the details of 11 patients seemed to have been copied and pasted repeatedly, suggesting that many of the patients in the trial may not have existed. The study authors claimed their data had been “rigged, sabotaged or mistakenly entered” and retracted the paper.

Fortunately, there is Cochrane, an international group widely recognized for its rigorous assessments of the medical literature in COVID-19 and far beyond. Last summer, Cochrane sifted through all the ivermectin “studies” it could find. It identified 14 randomized controlled trials of ivermectin that compared the drug with no treatment, the prevailing standard of care, or a placebo.

None of these studies, individually or when combined in a meta-analysis, showed that giving ivermectin to patients diagnosed with COVID-19 had any significant effect on preventing the need for mechanical ventilation or supplemental oxygen, viral clearance, clinical improvement, duration of hospital stay, or death. But since the certainty of the evidence was judged to be low, meaning that there were widespread problems with these 14 studies, Cochrane concluded that the efficacy and safety of ivermectin was still “uncertain.”

Not “uncertain” are the treatments for COVID-19 that current NIH guidelines recommend. For COVID-19 outpatients, the guidelines call for the use of the FDA-authorized antiviral drugs Paxlovid, remdesivir, or molnupiravir or the FDA-authorized monoclonal antibodies in sotrovimab. For hospitalized patients requiring supplemental oxygen or a ventilator, the guidelines recommend remdesivir or dexamethasone or a combination of the two drugs. Ivermectin is suggested only for preventing or treating Strongyloides (roundworm) infections in COVID patients, not for preventing or treating COVID-19 itself.

The myth of “miracle” ivermectin arrived in the United States late in 2020 where it fit in smoothly with the popular narrative of anti-vaccine activists.

But the unsettling revelations about the serious problems with ivermectin research didn’t slow down the drug’s bandwagon. The myth of “miracle” ivermectin arrived in the United States late in 2020 where it fit in smoothly with the popular narrative of anti-vaccine activists that the U.S. government and Big Pharma were pushing unnecessary, expensive, and dangerous vaccines on the public. But that sort of narrative needs a counter-narrative and ivermectin fit the bill. Here was a safe and inexpensive alternative that arrogant elites were withholding from the long-suffering public.

“Miraculous,” Wisconsin physician Pierre Kory called ivermectin at a U.S. Senate hearing in December 2020. “It basically obliterates transmission of this virus,” he testified. “If you take it, you will not get sick.” (As luck would have it, Kory later contracted COVID-19 himself despite using ivermectin every week.)

Video of Kory’s testimony was viewed eight million times before YouTube removed it for violating its policy against COVID misinformation. By then, ivermectin prescriptions had soared.

In 2021, Fox News personalities took up the cause. Ivermectin is “incredibly effective in treating COVID,” Maria Bartiromo told her viewers. Ivermectin is “good to take” and provides “enormous benefit,” Laura Ingraham gushed. It’s “used around the world to treat and prevent the spread of the coronavirus,” Tucker Carlson alerted his audience.

At least 60 ivermectin Facebook groups sprang up where members could trade information about sources of ivermectin, dosages, and sympathetic doctors. Facebook took down some of the groups, but others remain active.

Celebrities like controversial podcaster Joe Rogan spoke publicly about treating their COVID-19 illnesses with ivermectin (in his case, along with monoclonal antibodies combined with drugs unproven for COVID-19 like antibiotics and IV vitamin C).

Republican politicians also got into the act. Senator Ron Johnson of Wisconsin suggested that ivermectin “could have stopped the pandemic before we even had a vaccine.” Rand Paul, Senator from Kentucky and, unbelievably, a physician, claimed that it was hatred for Donald Trump stopping the government from studying ivermectin. Marjorie Taylor Greene, the controversial Georgia Congresswoman most recently known for cavorting with white supremacists, declared that anyone who blocked COVID patients from taking ivermectin has “blood on their hands.”

Matters got even nastier. Researcher Edward Mills of Canada’s McMaster University said he received death threats shortly after revealing at a U.S. NIH conference in August that a big clinical trial of ivermectin in Brazil had found no benefit. And David Boulware of the University of Minnesota found himself compared to Nazi doctor Josef Mengele for even trying to set up a clinical trial of ivermectin.

For others, however. the controversy over ivermectin is a goldmine. One of the leading pro-ivermectin (and anti-vaccine) groups is America’s Frontline Doctors, founded by Simone Gold, a California physician who recently pleaded guilty to entering the U.S. Capitol during the January 6th insurrection to deliver a speech denouncing vaccine mandates.

Her group began offering the public $90 to $150 telephone consultations with physicians who would prescribe ivermectin (medical insurance not accepted). Hacked records showed that during just two months in the summer of 2021, Gold’s group raked in $6.7 million in consulting fees and sold $4.7 million dollars of ivermectin to tens of thousands of individuals. In December, America’s Frontline Doctors announced it would be opening clinics to dispense ivermectin.

In an October 2021 survey, the belief that ivermectin is a safe and effective treatment for COVID-19 was held by 14 percent of the U.S. public.  That’s about the same percentage as those who believed in the same survey that you can contract COVID-19 from the COVID-19 vaccines and that the government is hiding deaths from the vaccines.

COVID-19 vaccines and treatments have become so politicized that people are now suffering needlessly and even dying simply because they’ve trusted the wrong people. Scarier still is the likelihood that this polarization may now be the new normal—one that in the future could cripple our national response when a new pandemic or other public health crisis inevitably emerges.