UK investigators say a drug reduced Covid-19 deaths for the first time. The world ponders what to do next
In the hours after UK investigators said that, for the first time, a drug had been shown to help prevent deaths in Covid-19 patients, a world of doctors, public health researchers and regulators were left trying to figure out what it meant and how to respond.
Britain’s NHS acted first, authorizing the drug, a generic steroid called dexamethasone, within hours of the study announcement. Praising the study’s investigators, the agency said the drug would become the new standard of care and available throughout the country.
“From today, the standard of treatment for Covid-19 will include dexamethasone, helping save thousands of lives while we deal with this terrible virus,” health secretary Matt Hancock said in a statement.
Elsewhere, though, the response was slower. Even as many doctors embraced the results as the first major breakthrough for severe Covid-19 patients — and arguably the biggest medical breakthrough since the start of the pandemic — others preached caution, at least until the full data were released. After scores of companies released data by press release rather than in publications, and earlier this month a pair of hydroxychloroquine studies were retracted from prestigious journals, they were wary of claiming success too soon.
“This is a highly reputable group — but still we need more information about the study,” Harlan Krumholz, a cardiologist and professor of medicine at the Yale School of Medicine, said in an email.
WHO inspector general Dr. Tedros Adhanom Ghebreyesus called the study “great news” and said they would move to revise treatment guidelines. They are waiting, though, to receive full details from the study and will conduct a meta-analysis “to increase our understanding of the intervention.”
The FDA wouldn’t comment on whether they would authorize dexamethasone. A spokesperson for the Infectious Diseases Society of America said they would include a “discussion” of the drug but not a recommendation in their next guidelines on April. “That will likely change as more research builds on their effectiveness,” they said.
The 6,000-person RECOVERY study, run by investigators at the University of Oxford, found that the cheap and widely-available steroid lowered the risk of death for patients on ventilators by about a third and for severely ill patients who only required oxygen by about a fifth. After the NIH remdesivir trial, it was the first randomized controlled study to show a drug could be effective and it was the first such trial to show a drug could reduce mortality.
“These UK recovery trial data are the real deal,” David Boulware, an infectious disease specialist at the University of Minnesota who led one of the first randomized hydroxychloroquine studies, told Endpoints News in an email.“This is the first therapy that has conclusive data demonstrating benefit in those critically ill ICU patients.”
Boulware said the data made it “pretty clear” who should get the drug, echoing comments yesterday from lead investigator Peter Hornby that dexamethasone should become the new standard of care for ICU patients.
Many doctors had already been giving patients dexamethasone off-label. Now it’s likely that even more will, said Ali Khan, the former director of the CDC’s Office of Public Health Preparedness, “given we were other using snake oil.”
Pointing to the mortality data, Memorial Sloan Kettering’s Peter Bach said on Twitter that for oxygenated patients, dexamethasone might be a better option than remdesivir. The NIH’s remdesivir study, results from which were announced at the end of April and published last month, showed improved time to recovery in some patients. That trial did not, however, prove the antiviral could boost survival for anyone, nor benefit ICU patients at all.
1) Dex but not Rem has convincing data on mortality (Rem has trend but not statistical consistency). 2) Dex is something clinicians know (I am wondering if PCP prophylaxis needed here) and Rem is not. 3) Dex is cheap, $GILD prob will ask >$5K per treatment for Rem, maybe more 5/n
— Peter B. Bach, MD (@peterbachmd) June 16, 2020
On Twitter, doctor, public health researcher, and writer Atul Gawande criticized the investigators. In light of recent retractions – including a pair of hydroxychloroquine studies pulled from The Lancet and the New England Journal of Medicine – he argued “it is unacceptable to tout study results by press release without releasing the paper.”
It will be great news if dexamethasone, a cheap steroid, really does cut deaths by 1/3 in ventilated patients with COVID19, but after all the retractions and walk backs, it is unacceptable to tout study results by press release without releasing the paper. https://t.co/ZP5GVMUCW3
— Atul Gawande (@Atul_Gawande) June 16, 2020
The retractions, though, had to do with faulty data from electronic medical records, rather than a randomized controlled study like the dexamethasone trial.
”Questions about COVID-19 studies using electronic data are irrelevant,” Khan, now a professor at the University of Nebraska Medical School, said in an email. He noted that the FDA authorized remdesivir 4 days after the topline results were announced — and nearly a month before the full data were published.
The results will also have implications for companies running trials on other Covid-19 drugs. A spokesperson for Regeneron told STAT yesterday that the trials for their Covid-19 antibodies have protocols that allow them to change the standard of care arm if new evidence arises. A spokesperson for Merck, which is testing an antiviral in humans, said “it is too early to speculate” on how the study could affect their trials.
“We look forward to reviewing the full results of the U.K. RECOVERY trial when they become available,” they said.
Like most drugs, dexamethasone is not without side effects. Jairam Lingappa, a professor of public health at the University of Washington and a CDC official during the SARS outbreak, said that if the study held up through peer review, the drug would be helpful but “wasn’t a final answer.” He noted that dexamethasone has been life-saving for several inflammatory conditions, including bacterial meningitis, but it can also lead to an increased risk of infection.
That makes it, he said, more of a stopgap while directly targeted drugs, such as certain antibodies and antivirals, go through development.
“Having something more specific for COVID will likely avoid some of those risks,” he wrote in an email. “But certainly it provides a helpful option in the face of disaster.”
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