Ivermectin for Covid-19 remains controversial

19 April 2021

In recent months there has been a lot of debate about the drug Ivermectin and how it could be used to treat or prevent Covid-19. One particular claim that gained a lot of attention was that the drug could reduce Covid-19 deaths by three quarters. This claim was based on a subsection of a review which involved a small handful of trials. 

There is a growing body of research on Ivermectin, some of which shows benefit, but there have been questions raised on the reliability of some of the  data provided in support of Ivermectin. 

Here we explain the debate, and why, at the time of writing, some countries are using it to treat or prevent Covid-19 and why others, like the UK, are not.

What is Ivermectin?

Ivermectin is an anti-parasite medication which is sometimes used as a treatment for infections like scabies as well as some forms of rosacea. It is generally considered to be a safe drug and is widely used, however, like many medications it does come with a small risk of serious side effects

There are also concerns about using Ivermectin in very unwell people, and in combination with other medications.

In addition, there have been reports of individuals using very high doses of veterinary grade Ivermectin, which is unsafe. 

Why might Ivermectin be useful for Covid-19?

Research has shown that in laboratory testing, rather than in humans, Ivermectin has an antiviral effect on a wide range of viruses. This includes RNA viruses, the same type of virus that causes Covid-19. 

Lab testing has also shown that Ivermectin effectively reduces replication of SARS-CoV-2 (the virus that causes Covid-19) in cells. However, the study that showed this used much higher doses of Ivermectin than would normally be used in humans. 

There have since been a large number of studies looking at Ivermectin in the treatment and prevention of Covid-19 in humans. Nineteen are currently listed as completed on the US National Library of Medicine database. 

Due to worsening rates of infection with Covid-19 and more frequent use of Ivermectin for parasites, countries like Brazil, Peru, and Bolivia started to use the treatment early on in the pandemic. In May 2020, the Bolivian Minister of Health commented that the treatment may be used under medical protocol with informed consent, but “does not have scientific validation in the treatment of coronavirus”. Ivermectin was also recently approved for use in some capacity against Covid-19 by Honduras and Slovakia in January 2021, and the Czech Republic in March.

Despite inconsistencies in the data, clinicians and policy-makers in some countries have decided that there is enough evidence of a clinical benefit to use the drug, especially in the context of a pandemic.

Others, including regulatory bodies such as the World Health Organisation (WHO) and the European Medicines Agency (EMA), have argued that much of the initial data was observational and showed association rather than causation. They have suggested that although there are now a large number of trials looking at Ivermectin and Covid-19, many of these offer low levels of evidence and do not prove it works. The WHO, for example, cites uncertainty and imprecision amongst many of the studies. For example, some of the studies did not conceal who received Ivermectin and who received a placebo. They also had unclear enrollment and randomisation practices, and a lack of detail around treatment plans. 

Because there was also a low number of deaths associated with the studies, the WHO suggested caution in interpreting generalisable conclusions about the impact that Ivermectin has on mortality. They demonstrated for example, that in their meta analysis, a difference of three deaths would make the benefit that Ivermectin appeared to have regarding mortality statistically insignificant. Critics of this review, argue that the WHO did not include all the relevant studies in their analysis, particularly around mortality outcomes. They also question the way that the WHO have categorised some of the data. 

There are other concerns about the harms of using Ivermectin without being sure that it works, including adverse effects, drawing clinicians away from treatments with known benefits, and reduced availability of Ivermectin for other clinical needs. 

Why isn’t the UK using ivermectin?

The Department of Health and Social Care confirmed to Full Fact that based on the data currently available, it did not believe that there is sufficient evidence to prove that Ivermectin is a safe and effective treatment for Covid-19. 

But it did confirm that the Therapeutics Taskforce continues to monitor worldwide data on the drug and keep this decision in review. The UK Covid-19 Therapeutics Advisory Panel has not chosen Ivermectin for further investigation in UK trials, choosing instead to investigate candidates it felt were more promising.

The UK Principle trial, which is aiming to “find treatments for COVID-19 for people in the community who are at higher risk of complications”, told Full Fact that it is exploring the potential of including Ivermectin in its work.

Merck, one company that produces Ivermectin, said in February 2021 that it had examined the findings of “all available and emerging studies of ivermectin for the treatment of COVID-19”, and the analysis has concluded that there was:

  • “No scientific basis for a potential therapeutic effect against COVID-19 from pre-clinical studies; 
  • “No meaningful evidence for clinical activity or clinical efficacy in patients with COVID-19 disease, and; 
  • “A concerning lack of safety data in the majority of studies.”

In March 2021, the World Health Organisation (WHO) reviewed the evidence and concluded that Ivermectin should only be offered as treatment for Covid-19 as part of controlled clinical trials. It said this was because of low quality evidence as to its efficacy.

The EMA announced a similar position the same month.

Where did the claim that Ivermectin could reduce deaths by three quarters come from?

In early 2021, several sources publicised a figure which stated that Ivermectin could reduce deaths by 75%. The figure comes from a meta analysis (a review of multiple studies) conducted by the International Ivermectin Project Team, which included data from 18 randomised control trials where participants are randomly assigned into different groups to assess the impact of a particular treatment). The analysis looked at a variety of different outcomes including how quickly participants’ immune systems were able to remove the virus, hospital stay duration, as well as mortality data. 

The 75% reduction in deaths figure is taken specifically from analysing mortality data from six randomised control trials using Ivermectin. There were 14 deaths among the 650 people given the drug compared with 57 deaths out of 597 people who did not receive it.  

However, the authors noted that many of the trials were small, not peer-reviewed and used other treatments in addition to Ivermectin. The studies did not always conceal who was having treatment and who was having placebo (which leaves room for bias), and Ivermectin was tested on a mixture of severe and mild cases of Covid-19. They also commented that there were wide variations in standards of care, doses of medication used,  and durations of treatment. The authors also noted the potential for publication bias (because often only successful trials will be published or more broadly circulated) skewing the larger review. 

The authors therefore concluded that although the initial review was promising, further investigation with large, high quality and appropriately controlled randomised control trials were required.

 

 

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