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The National Institutes of Health (NIH) has dropped its recommendation against the inexpensive antiparasitic drug ivermectin for treatment of COVID-19, and the agency now advises it can't recommend for or against its use, leaving the decision to physicians and their patients.
"Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment of COVID-19," according to new NIH guidance released last week.
Passionate arguments have been waged for and against the drug's use.
The NIH update disappointed members of the Front Line COVID-19 Critical Care Alliance (FLCCC), which outlined its case for endorsing ivermectin in a public statement on Monday. Point-by-point, the group of 10 physicians argued against each limitation that drove the NIH's ruling.
The group's members said that although grateful the recommendation against the drug was dropped, a neutral approach is not acceptable as total US deaths surpassed 400,000 since last spring — and currently approach 4000 a day. Results from research are enough to support its use, and the drug will immediately save lives, they say.
"Patients do not have time to wait," they write, "and we as healthcare providers in society do not have that time either."
NIH, which in August had recommended against ivermectin's use, invited the group to present evidence to its treatment guidance panel on January 6 to detail the emerging science surrounding ivermectin. The group cited rapidly growing evidence of the drug's effectiveness.
Pierre Kory, MD, president/cofounder of FLCCC and a pulmonary and critical care specialist at Aurora St. Luke's Medical Center in Milwaukee, also spoke before a Senate panel on December 8 in a widely shared impassioned video, touting ivermectin as a COVID-19 "miracle" drug, a term he said he doesn't use lightly.
Kory pleaded with the NIH to consider the emerging data. "Please, I'm just asking that they review our manuscript," he told the senators.
"We have immense amounts of data to show that ivermectin must be implemented and implemented now," he said.
Some Draw Parallels to Hydroxychloroquine
Critics have said there's not enough data to institute a protocol, and some draw parallels to another repurposed drug — hydroxychloroquine (HCQ) — which was once considered a promising treatment for COVID-19, based on flawed and incomplete evidence, and now is not recommended.
Paul Sax, MD, a professor of medicine at Harvard and clinical director of the HIV Program and Division of Infectious Diseases at Brigham and Women's Hospital in Boston, wrote in a blog post earlier this month in the New England Journal of Medicine Journal Watch that ivermectin has more robust evidence for it than HCQ ever did.
"[B]ut we're not quite yet at the 'practice changing' level," he writes. "Results from at least 5 randomized clinical trials are expected soon that might further inform the decision."
He said the best argument for the drug is seen in this explanation of a meta-analysis of studies of between 100 and 500 patients by Andrew Hill, MD, with the Department of Pharmacology, University of Liverpool, United Kingdom.
Sax advises against two biases in considering ivermectin. One is assuming that because HCQ failed, other antiparasitic drugs will too.
The second bias to avoid, he says, is discounting studies done in low- and middle-income countries because "they weren't done in the right places."
"That's not just bias," he says. "It's also snobbery."
Ivermectin has been approved by the US Food and Drug Administration (FDA) for treatment of onchocerciasis (river blindness) and strongyloidiasis, but is not FDA-approved for the treatment of any viral infection. It also is sometimes used to treat animals.
In dropping the recommendation against ivermectin, the NIH gave it the same neutral declaration as monoclonal antibodies and convalescent plasma.
Some Physicians Say They Won't Prescribe It
Some physicians say they won't be recommending it to their COVID-19 patients.
Amesh Adalja, MD, an infectious disease expert and senior scholar at the Johns Hopkins University Center for Health Security in Baltimore, Maryland, told Medscape Medical News that the NIH update hasn't changed his mind and he isn't prescribing it for his patients.
He said although "there's enough of a signal" that he would like to see more data, "we haven't seen anything in terms of a really robust study."
He noted that the Infectious Diseases Society of America (IDSA) has 15 recommendations for COVID-19 treatment "and not one of them has to do with ivermectin."
He added, "It's not enough to see if it works, but we need to see who it works in and when it works in them."
He also acknowledged that "some prominent physicians" are recommending it.
Among them is Paul Marik, MD, endowed professor of medicine and chief of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk. A cofounder of FLCCC, Marik has championed ivermectin and developed a protocol for its use to prevent and treat COVID-19.
The data surrounding ivermectin have met with hope, criticism, and warnings.
Australian researchers published a study ahead of print in Antiviral Research that found ivermectin inhibited the replication of SARS-CoV-2 in a laboratory setting.
The study concluded that the drug resulted post-infection in a 5000-fold reduction in viral RNA at 48 hours. After that study, however, the FDA in April warned consumers not to self-medicate with ivermectin products intended for animals.
The NIH acknowledged that several randomized trials and retrospective studies of ivermectin use in patients with COVID-19 have now been published in peer-reviewed journals or on preprint servers.
"Some clinical studies showed no benefits or worsening of disease after ivermectin use, whereas others reported shorter time to resolution of disease manifestations attributed to COVID-19, greater reduction in inflammatory markers, shorter time to viral clearance, or lower mortality rates in patients who received ivermectin than in patients who received comparator drugs or placebo," the NIH guidance reads.
The NIH acknowledges limitations: the studies have been small; doses of ivermectin have varied; some patients were taking other medications at the same time (including doxycycline, hydroxychloroquine, azithromycin, zinc, and corticosteroids, which may be potential confounders); and patients' severity of COVID was not always clearly described in the studies.
Nasia Safdar, MD, medical director of infection prevention at the University of Wisconsin Hospital in Madison, told Medscape Medical News she agrees more research is needed before ivermectin is recommended by regulatory bodies for COVID-19.
That said, Safdar added, "in individual circumstances if a physician is confronted with a patient in dire straits and you're not sure what to do, might you consider it? I think after a discussion with the patient, perhaps, but the level of evidence certainly doesn't rise to the level of a policy."
A downside of recommending a treatment without conclusive data, even if harm isn't the primary concern, she said, is that supplies could dwindle for its intended use in other diseases. Also, premature approval can limit the robust research needed to see not only whether it works better for prevention or treatment, but also if it's effective depending on patient populations and the severity of COVID-19.
Adalja and Safdar have disclosed no relevant financial relationships.
Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News and Nurse.com and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick
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Cite this: Controversy Flares Over Ivermectin for COVID-19 - Medscape - Jan 20, 2021.