Reality check: There’s still no compelling evidence for ivermectin as a treatment for COVID-19

Reality check

From Federal MP Craig Kelly to tennis champion Pat Cash, ivermectin has attracted attention around the world as a potential treatment for COVID-19.

But the medicine, used in Australia to treat parasitic infections and skin conditions, is not the coronavirus wonder drug its proponents say it is: there is no compelling evidence to demonstrate that it is safe to use in the treatment or prevention of COVID-19.

Both Australian and overseas regulators have not approved its use for the coronavirus and warn it may endanger the health of those who take it.

The drug’s manufacturer, Merck, has also said it should not be used to treat or prevent COVID-19.

How then, did ivermectin become the drug of the moment? In this reality check, RMIT ABC Fact Check dives into the scientific evidence for ivermectin as a COVID-19 treatment, and explores how its use came to be a political talking point.

What is ivermectin?

Ivermectin, sold in tablet form and marketed as Stromectol by pharmaceutical company Merck, is a prescription medication used in Australia as a treatment for parasitic infections such as onchocerciasis (river blindness), intestinal strongyloidiasis (roundworm) and scabies.

In cream form, ivermectin is sold by Galderma under the name Soolantra and is used to treat the skin condition rosacea, while in other countries, such as the US, the drug is also used to treat head lice.

In animals, ivermectin is commonly used to treat parasites, according to the Australian Veterinary Association, which noted in a media release that ivermectin preparations for animals “are very different from those approved for human use”.

Ivermectin in the news

Recent weeks have seen a rise in international interest in the use of ivermectin to treat and prevent COVID-19, despite a lack of evidence for its effectiveness and the efforts of both Australian and overseas health authorities in issuing warnings about the drug.

In Australia, the Guardian reported that the country had experienced a national shortage of ivermectin and seen a more-than-tenfold increase in imports of the drug in August.

In the Northern Territory, a handful of people seeking ivermectin after reading about the treatment on social media forced local health officials to warn against self-medicating with the drug, according to an ABC report.

And in NSW, the improper use of ivermectin has been reported to have led to at least one overdose.

On September 1, the Western Sydney Local Health District reported that a COVID-19 positive Sydney man had presented to hospital after overdosing on ivermectin and other treatments sourced online.

Westmead Hospital toxicologist Naren Gunja said while the self-administered treatment had not led to severe toxicity, it “didn’t help their COVID either”.

In the US, meanwhile, the FDA was forced to release a statement in late August explaining why ivermectin should not be used to treat or prevent COVID-19, urging in an accompanying tweet:

“You are not a horse. You are not a cow. Seriously, y’all. Stop it.”

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That warning came after the Mississippi State Department of Health revealed that at least 70 per cent of calls to its poison control centre “related to ingestion of livestock or animal formulations of ivermectin purchased at livestock supply centers”, while calls to the Texas Poison Control Network relating to ivermectin increased by 591 per cent when compared to the previous year.

The early evidence for ivermectin as a COVID-19 treatment

According to the most up-to-date science, there is not enough evidence to conclude that ivermectin is an effective COVID-19 treatment.

Early research, however, showed promising signs for the drug.

Ivermectin’s potential as a COVID-19 treatment came via two studies which found that the drug worked as an inhibitor of SARS-CoV-2 in vitro and led to lessened symptoms and severity of COVID-19 in animals.

The first study, published by Australian researchers in April 2020, found a single dose of ivermectin in vitro was “able to control viral replication” of SARS-CoV-2 (the virus which causes the disease COVID-19) within 24 to 48 hours.

That finding, however, applied only to cells studied in a lab, with the researchers noting that further investigation was needed in order to determine possible benefits in humans.

“Altogether the current report, combined with a known-safety profile, demonstrates that ivermectin is worthy of further consideration as a possible SARS-CoV-2 antiviral,” the study concluded.

The second study, published in November 2020, concluded that ivermectin “reduced clinical deterioration” in COVID-19 positive hamsters.

Writing for the Conversation, Andrew McLachlan, the dean of pharmacy at the University of Sydney, noted that both studies involved “very high concentrations” of ivermectin that were “many times higher than can be achieved in the body at doses recommended to treat parasites”.

What we know now

Since those promising early studies, strong evidence that ivermectin could work to treat or prevent COVID-19 has failed to materialise.

In its August 20 statement on the COVID-19 treatments, the TGA pointed to a systematic review of the scientific evidence for ivermectin as a coronavirus treatment published by the Cochrane Library in July of this year.

In an email, Professor McLachlan told Fact Check he rated this study “as the best that is currently available”.

“The Cochrane Review probably represents the most rigorous interrogation and critical appraisal of the available evidence to guide our understanding of (the limited) role of ivermectin in treating and prevention of COVID-19,” he said.

Gideon Meyerowitz-Katz, an epidemiologist at the University of Wollongong, agreed.

“At this point I’d say that the Cochrane review is the highest-quality evidence out,” Mr Meyerowitz-Katz told Fact Check in an email. “While it has not yet been updated with some of the newer trials, Cochrane is the gold standard in medical research and very trustworthy.”

“Their review into ivermectin is extremely impressive and well done.”

The Cochrane reviewers concluded that “based on the current very low- to low-certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent COVID-19”.

“The completed studies are small and few are considered high quality,” the reviewers said, adding that several studies were underway that “may produce clearer answers in review updates”.

“Overall, the reliable evidence available does not support the use of ivermectin for treatment or prevention of COVID‐19 outside of well‐designed randomized trials.”

Another systematic review, which Professor McLachlan pointed to in his article for the Conversation, found that the drug did not work to reduce mortality, length of hospital stay or viral clearance in patients with COVID-19.

It also didn’t have an effect of adverse events or severe adverse events associated with COVID-19.

Meanwhile, two studies often cited as proof of ivermectin’s effectiveness in preventing and treating COVID-19 have been flagged by experts as being potentially fraudulent.

The first study, from Argentina, supposedly found the drug to be 100 per cent effective in preventing the disease.

But according to a report from Buzzfeed News, “numbers, genders, and ages of the study’s participants were inconsistent” and a hospital supposedly involved in the study, as well as health officials in Buenos Aires, had “no record of it happening”.

Hector Carvallo, the researcher overseeing the project, has also refused to share his data widely, including with one of his own collaborators.

Mr Meyerowitz-Katz, who was one of the experts who issued warnings about the Argentinian study, also found a now-retracted pre-print study by a group of doctors in Egypt to be problematic.

Writing on Medium, Mr Meyerowitz-Katz explained how the study — which claimed to show that COVID-19 patients treated with ivermectin were 90 per cent less likely to die than those who received a placebo — relied on the wrong statistical methods and a methodology “filled with holes”.

Speaking to Fact Check, Mr Meyerowitz-Katz said there were two main issues with the study.

“Firstly, the dataset uploaded to the preprint server that the authors claimed was the data used in the study was fake,” he explained. “Secondly, the study itself had a great deal of plagiarism in it as well.”

According to Mr Meyerowitz-Katz’s Medium post, around one third of the people “involved” in the study were already dead when the researchers started their recruitment process, 25 per cent were already hospitalised and one group of patients seemed to be clones of one another.

“I don’t know for sure that this study is fraudulent, and perhaps we never will,” Mr Meyerowitz-Katz wrote.

“But we do know that no one should ever have used it as evidence for anything regardless.”

What the health authorities say

In light of the current science, the TGA has not approved ivermectin for use to treat or prevent COVID-19, and says more evidence is needed before it “could be considered a safe and effective treatment option”.

“Although there are some studies published either on unreferenced websites or in lower-tier medical journals, the consensus view of major regulators and in top-tier international medical journals is that the evidence for the clinical efficacy and safety of ivermectin for the treatment or prevention of COVID-19 is not strong at this stage,” the administration said in an August 20 statement on its website.

The administration’s decision not to approve the drug is in part based on the recommendation of the National COVID-19 Clinical Evidence Taskforce, which is made up of a large group of independent clinical experts who are “continuously updating treatment recommendations based on the best available evidence”.

The taskforce, which conducts daily searches to identify relevant high-quality studies, recommends ivermectin not be used to treat COVID-19 outside of “randomised trials with appropriate ethical approval”.

“There is currently limited evidence about the impact of ivermectin on patient-relevant outcomes in the treatment of COVID-19, the taskforce’s guidelines for the clinical care of people with COVID-19 reads.

“The panel has significant concerns regarding the potential harms of unproven treatments.”

Similar recommendations, that ivermectin only be used to treat COVID-19 in trials, have also been made by the World Health Organisation, the US Food and Drug Administration and the European Medicines Agency.

The drug’s manufacturer, Merck, has also warned against using ivermectin to treat or prevent COVID-19, citing a lack of scientific evidence for its use and a “concerning lack of safety data in the majority of studies.