Ivermectin Shows No Clear Benefit in the Treatment of Covid-19

Ivermectin is a horse dewormer and anti-parasitic medication that has been promoted across the world for the treatment of Covid-19. It has been in the news a lot recently because a large portion of the evidence base for the drug appears to have been based on fraudulent research, which, as scientific rigor goes, is usually considered to be a bit of an issue.
But we’ve held out hope that the drug works for Covid-19 because, despite the foundations of the research being cracked, there were still a number of positive trials, and some of them were really well done. Yes, fraud is bad, but we can’t throw the baby out with the bathwater just because one study may never have happened at all.
Until today. The results from a very large new study were just released, showing absolutely no benefit for ivermectin when compared with a placebo pill. It now seems depressingly likely that ivermectin is probably not useful for treating Covid-19.
The new study in question is called the Together Clinical Trials, and it’s a truly amazing collaboration between a number of universities and research groups to study the effects of repurposed drugs on people with Covid-19 who attend hospitals as outpatients.
Basically, they look at people who are at moderate risk but are experiencing relatively mild disease, randomize them to either get one of several drugs or a placebo, and then see if those drugs have any benefit in treating Covid-19. The full protocol is a masterpiece of science—well worth reading if you’re interested in trial design.
This trial has already demonstrated that hydroxychloroquine and lopinavir/ritonavir are unlikely to be beneficial treatments for people with Covid-19 in outpatient settings and, because of the hype around ivermectin, had included the drug in a treatment arm to see if it worked. The results from that part of the trial, including over 1,300 patients, were released in summary form late this afternoon.
They showed no benefit for ivermectin in the treatment of Covid-19. None whatsoever.
Pictured: Results from the slide deck. Source: Together Clinical Trials
Now, it’s worth noting that these are not the final results — the authors have released a slide deck along with a lengthy presentation, but we don’t have an actual published version of the study yet.
That being said, the protocol is available online, and the study itself is a very impressive work of science. In a high-quality study of over 1,300 people, the researchers found that giving ivermectin to people who had mild disease did not reduce the risk of hospitalization or death at all. This is the largest and best trial conducted on ivermectin to date. That makes the finding pretty solid and very disappointing for all of us who hoped that ivermectin really was effective against Covid-19.
So these results showed no benefit for ivermectin. That’s very useful, but it raises another question: What does this mean for the ivermectin literature as a whole?
I’ve previously written about the ivermectin literature, looking at the meta-analyses of the drug to see what the benefit for mortality is (i.e., how much it reduces the risk of dying). This means that I luckily have a great baseline that can easily be updated to include this new study as well as one other trial that has come out recently on ivermectin and Covid-19. The results are, unfortunately, not very good — ivermectin may offer everything from a modest benefit to a modest harm in the treatment of people with Covid-19.

I used the studies from Bryant, et al. and the same model replicated in Stata 15.0, which is an inverse-variance model with random effects. I took out the potentially fraudulent Elgazzar study and extremely low-quality Niaee study and added the newer Vallejos paper as well as the Together Clinical Trials.
The numbers on the bottom of that forest plot pretty much say it all — with no heterogeneity, there is no evidence of a benefit for ivermectin on the treatment of Covid-19 in this statistical model. The confidence interval runs from a 43% benefit to a 14% detriment, meaning that ivermectin may either be good for your health or increase your risk of death based on the studies included.
I’m still hopeful that ivermectin has some benefit. It’s plausible, based on these results, that the drug reduces the risk of dying by a modest amount (in the range of 10%), which is still a really good intervention even if it’s not the miracle some were hoping for. But it is really not possible to say that with any certainty yet, and the biggest and best trials appear to paint a very depressing picture of ivermectin having no benefit. It’s entirely possible — perhaps even likely — that ivermectin is totally useless in the treatment of Covid-19. Given that the drug has been taken by tens, if not hundreds, of millions of people to treat their Covid-19 worldwide, that’s a really unfortunate finding to be faced with.
There is a slight silver lining to this new trial. Fluvoxamine, another cheap repurposed medication, showed quite impressive benefits on the risk of hospitalization. While there was no improvement seen in people’s risk of death, it still points toward fluvoxamine potentially being a very effective treatment for people with early or mild Covid-19, which is a truly fantastic finding.
So while we can all commiserate over the fact that ivermectin is looking less and less likely to be effective, we can celebrate both the amazing researchers who’ve done this work and the increasing likelihood that fluvoxamine could actually be a very useful drug for Covid-19. This is the first good trial to show such a benefit, but as I said, it was big and a very solid piece of work, so it’s looking likely that the fluvoxamine is indeed effective just as it’s looking likely that ivermectin is not.
As before, it’s still possible that ivermectin works, and I sincerely hope that I’m proven wrong. But as the evidence stands now, it really doesn’t look good.

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