Old Dogs Can Learn New Tricks: Is Outpatient Remdesivir a Game Changer Against Omicron?
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With this podcast, we recap innovative, practice changing studies in ten minutes or less. And remember, nothing here is medical advice; we just present the evidence and our (sometimes hot) takes.
Old Dogs Can Learn New Tricks: Is Outpatient Remdesivir a Game Changer against Omicron?
We’re two years into this pandemic and seeing higher case numbers than ever before. The virus has changed the game, mutating into a hyper-transmissible new variant deemed “Omicron”. Despite this bleak outlook, there’s room for hope too. The Omicron variant may be causing less severe disease, and we’ve got some new therapies to combat it as well. With all its spike protein mutations, its negated some, but not all of our monoclonal antibodies. Fortunately, we’ve got some new oral antivirals like Paxlovid that shouldn’t be affected by this new variant. But as many of you know, it can be darn hard to get your hands on Paxlovid these days and Sotrovimab, the only monoclonal that seems to work against Omicron, is also in short supply. So, what about going back to our old workhorse at the start of the pandemic-Remdesivir?
Well, that’s exactly what some researchers did. They conducted a double blind, randomized controlled trial across various international sites including the US. They compared remdesivir vs placebo in over 500 high risk outpatients with COVID-19 and symptom onset within 7 days. Patients received either a 3 day course of IV remdesivir or placebo, and the primary outcome was a composite of COVID-19 related hospitalization or death from any cause.
A few things to keep in mind before we get to the results. First and foremost, the study excluded vaccinated individuals! Keep this in mind because this means the group we are looking at is the highest of high risk in terms of having poor outcomes from COVID-19. To be in the study patients had to have ANY of the following characteristics: be 60 years of age or older, obese, or have at least one comorbidity such as hypertension, diabetes or chronic kidney disease to name a few. The researchers also did a good job with stratifying randomization to keep key baseline characteristics similar between groups. They stratified by residence in a skilled nursing facility, age over or under 60 and whether patients resided in the US or Internationally.
So let’s see what good old remdesivir did for these high risk patients. At day 28, there was a statistically significant 87% relative risk reduction and 4.6% absolute risk reduction in the risk of COVID-19 related hospitalization or death from any cause. This means that just over 21 high risk, un-vaccinated patients would need to be treated with a 3-day course of IV remdesivir to prevent one COVID-19 related hospitalization or death.
Believe it or not, no patients died in either group, so really what we’re talking about here is a decrease in hospitalizations. Remdesivir also decreased COVID-19 related doctor visits by over 80%. There was no increase in adverse events seen with remdesivir either.
So, the question here is, does outpatient remdesivir add value in our fight against COVID-19? We think it does. We know from previous trials its shown efficacy in hospitalized patients who need supplemental oxygen. And it seems to be better the earlier in the course of COVID-19 infection it’s given. We know that COVID-19 illness has a predictable pattern. The early course is dominated by viral replication and damage from the virus itself. But as the body begins to control the virus, the immune system takes over and can become hyper-responsive. This is when our own immune system can start to cause damage when trying to fight the virus. So, if we know remdesivir works by stopping viral replication, why not jump out of the hospital setting and start giving this to outpatients as soon as they test positive?
This study adds strong evidence that this approach should be considered. It’s not as convenient as oral Paxlovid, but it doesn’t have the drug interaction issues that could make Paxlovid a tough choice for certain patients. It also may be more convenient than monoclonal antibodies. It can be stored at room temperature and doesn’t require post infusion monitoring for reactions like some of our monoclonals do. And now that Sotrovimab is the only monoclonal antibody available with efficacy against Omicron, it’s darn hard to get! The NIH guidelines recently endorsed outpatient remdesivir if both Paxlovid and Sotrovimab are unavailable or can’t be used.
And last but not least, we’d all do well to remember that remdesivir targets the highly conserved viral RNA polymerase. Most of the mutations that are making Omicron so difficult to deal with are in its spike protein. So, we do expect remdesivir to retain activity against this new variant.
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