Misinformation 5 – Ivermectin’s false dawn

Summary

• Ivermectin is a useful drug for specified helminth (worm) infections.
• Claims of phenomenal cure rates have been publicised by FLCCC, Mercola and others.
• The evidence from decent controlled trials does not support its use.
• Ivermectin is, like HCQ, a false dawn and its widespread use could cause potential harm.

Fresh off the Mercola production line and promoted by FLCCC, a small American group of doctors, claims are being made that the prescription of Ivermectin can prevent 70% of deaths due to COVID19. Wow!! – you might think – is this the final frontier? Or just another false dawn to mirror the fuss over the ineffective hydroxychloroquine.

So what is being claimed?

Ivermectin is an anti parasitic drug used occasionally for years to treat rare conditions like river blindness and other uncommon conditions. It works by interfering with nerve and muscle function in worms and insects. A leap of faith was born when evidence from Australia that it slowed dow viral replication in infected cells in the lab, albeit with doses which were vastly in excess of that tolerable by humans. This led to an early well conducted study which showed no benefit for Ivermectin on mild disease. Calls for more trials led, as so often is the case, to the chaos of lots of disorganised small scale low quality studies which fail to answer the seemingly simple question, does Ivermectin work?

The FLCCC is a controversial group of ten US doctors, led by Pierre Kory and Paul E. Marik. Kory is not known for his modesty. He opened his submission to evidence he presented to the US senate with the statement: “I want to start by saying that I am part of a group of physicians which include several of the most highly published and well-known critical care experts in the country and world”. Their evidence was rejected. They came to prominence after publishing a paper on Ivermectin which was withdraw by Frontiers in Medicine due to it “containing unsubstantiated claims and violated the journal’s editorial policies”. Of course this was then said to be “censorship”; sour grapes for being on the wrong side of fashioned peer review.

The FLCCC ploughed on and have produced an online interview to support their case. Tess Lawrie, who runs an independent consultancy has also produced interviews to pretty much the same effect. Mercola then jumps on the bandwagon. On viewing them, I get a sense of deja vu. They appear convincing and produce lots of impressive looking data to support their case. What they don’t do however, is explain the weaknesses in the studies they quote and they fail to produce evidence that does not support their case. If what they say is believed, they leave the viewer with feelings of frustration and anger that the “Powers That Be” could ignore their powerful arguments and commit multitudes of people with COVID19 to unnecessary deaths. Hummm….

The full picture

When it comes to medications, Randomised Controlled Trials (RCT) are not just the gold standard, they are pretty much the only way to sort out the useful wheat from the useless or even dangerous chaff. While the pandemic is an emergency, research falling short of high standard would risk treating millions of ill people with worthless and potentially harmful drugs. There are regulatory agencies who have looked at Ivermectin closely, so what have they found?

The US National Institute for Health reviewed the evidence as recently as February this year and found that the best RCT’s they could find failed to show any benefit for Ivermectin.

The Infectious Disease Society of America also reviewed the evidence and while they found some evidence of benefit, the quality of evidence was poor and they reported bias in some trials with positive results. They suggest that Ivermectin only be used in the context of clinical trials.

The WHO also reviewed the evidence on the basis of the best trials they could find, involving 500 people – again no significant benefit was found. The table below shows their results, which to me are quite clear, Ivermectin is not that useful for COVID19.

Here in Europe the EMA have recommened agianst its use, concluding: “Results from clinical studies were varied, with some studies showing no benefit and others reporting a potential benefit. Most studies EMA reviewed were small and had additional limitations, including different dosing regimens and use of concomitant medications. EMA therefore concluded that the currently available evidence is not sufficient to support the use of ivermectin in COVID-19 outside clinical trials.”

In the UK, the BMA have published a substantial “living systematic review” which is updated regularly as the evidence piles in and in the case of Ivermectin, they analysed 7 trials involving 700 people which showed the its role as Ivermectin to be “very uncertain”.

The scientists in the RECOVERY trial responsible for defining the place of most COVID19 treatments considered the evidence of benefit from Ivermectin so weak they did not want to use it in their bank of trials.

Of course, cynics will not accept the findings of these groups, but for me they pretty convincingly demonstrate that there is not significant benefit from Ivermectin. If you want to see this as ‘Big Pharma’ wanting simple and cheap medicines to be suppressed to protect their profits then I will hardly be able to change your mind, but the evidence fails to show any real benefits as things stand, and I personally feel that if there were any significant benefits, they would have surfaced by now. Improve outcome by 70%? Total nonsense.

Harms.

Using Ivermectin for critically ill patients who would be on a combination of drugs needed for their care, including steroids, is potentially dangerous and there is very little experience of its use in this context. To claim it is ‘safe and effective” due to experience with treating parasites is irresponsible.

A very current example of the plaque of injudicious prescribing is tragically playing out in India. There mucormycosis, a really difficult condition to manage, is becoming more common due to overuse of steroids. This shows how care is needed to prescribe the right drug for the right condition at the right time. Ivermectin may not have the same potential for harm as steroids, but treating millions of people without solid evidence is one big step on the way to doing real harm.

Curiously, one billion people are currently infected with helminths and they could even be of benefit in terms of immunity against COVID19. If so, mass prescription of anti-helminths like Ivermectin could paradoxically make COVID19 worse – another good reason to stick with results of decent trials and the analyses of regulators before rushing in.

WHO also point out the spurious nature of the “widely available cheap drug” claim. For one thing, its wide prescription for COVID19 would make it harder to obtain for the conditions it effectively treats. Resources and funds would be diverted to its manufacture and distribution in resource poor nations. Thought said to be well tolerated in most cases, like any medication, it is not without harms – side effects copied from the British National Formulary include:

“abnormal sensation in eye; anaemia; appetite decreased; asthenia; asthma exacerbated; chest discomfort; coma; confusion; conjunctival haemorrhage; constipation; diarrhoea; difficulty standing; difficulty walking; dizziness; drowsiness; dyspnoea; encephalopathy; eosinophilia; eye inflammation; faecal incontinence; fever; gastrointestinal discomfort; headache; hepatitis; hypotension; joint disorders; leucopenia; lymphatic abnormalities; Mazzotti reaction aggravated; myalgia; nausea; oedema; pain; psychiatric disorder; seizure; severe cutaneous adverse reactions (SCARs); stupor; tachycardia; tremor; urinary incontinence; vertigo; vomiting”

It’s certainly not a matter of cost. Dexamethasone has been show to prevent deaths in about a third of people with COVID19 facing ITU. The large scale studies have produced positive results and established the exact place of the steroid in the treatment of COVID19. To counter the claim that cheap drugs are avoided, dexamethasone is itself actually pretty cheap.

Back in the real work

Lacking our regulatory oversight, and desperate for anything that can help, South America’s Ivermectin prescribing has become widespread on the basis of reports of benefits which came from a very dubious commercial outfit called Surgisphere, whose dubious research has since been discovered to be a scandal. There are harms being done, as I mentioned about in terms of cost, displacement of a useful therapy for treatable conditions, side effects and false hope.

In South Africa, prescribing is chaotic and at times desperate. A recent review of the situation there concluded that advocating for “the supposed benefits of an unproven therapeutic when the sole justification is the desperation of the situation and the relative “safety” of the drug is inherently dishonest and hence ethically problematic” I couldn’t agree more.

Conclusion

It just depends how you look at things.

If you like what they say, then for you that might be that. Over here in the UK anger and irritation will follow given that the miracle treatment will be denied to you by those pesky doctors who actually are responsible for prescribing the drug.

Yet it’s really important to look further if you want to find out what is really happening and come to a reasoned conclusion. It is beyond most of us to look at each of the trials closely, and critically so the summaries by all the expert bodies are really useful. You will find that at best, Ivermectin might be worthy of further study, but any benefit is likely to be hard to find. If I get COVID19 right now, I would not want it.

If you believe the regulatory bodies, peer reviewed journals, science magazines, or even little old me, there seems to be pretty good consensus that Ivermectin for COVID19 is, like hydroxychloroquine, is another false dawn.

But I would say that, wouldn’t I!

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