Quebec-led study on colchicine drug dials back the hype on its ability to treat COVID-19
MONTREAL -- A drug some researchers claimed to be incredibly promising in treating COVID-19 is, according to the peer-reviewed research, potentially promising.
A Quebec-led international study that tested the drug colchicine as a treatment for non-hospitalized COVID-19 patients was published Thursday in The Lancet Respiratory Medicine Journal.
The full study comes about four months after meagre preliminary results were enthusiastically announced in a press release.
In contrast, the peer-reviewed manuscript of the COLCORONA study -- much anticipated by scientists around the world -- issued rather lukewarm recommendations, including the need to replicate “studies such as this one.”
It concludes that the anti-inflammatory medication colchicine, which is already easily available, “could” be used to treat certain patients, “given the absence of orally administered therapies to prevent COVID-19 complications."
The principal investigator said he stands by his original assessment of the drug, but other researchers said they aren't so sure.
“I believe the final paper is even stronger than what we presented initially, and some of the misconceptions, hopefully, have been clarified," said Dr. Jean-Claude Tardif of the Montreal Heart Institute and the study’s principal investigator.
But Dr. Emily McDonald, a researcher at the MUHC’s research institute who's been following the colchicine science, said she's not as enthusiastic.
“My view hasn't changed very much since the preprint came out -- it's similar numbers,” McDonald said after reviewing the Lancet article.
"I can't see it [colchicine] being useful for a lot of Canadians at this point,” she said.
The results of the research were not statistically significant for those who took colchicine and didn’t have confirmed diagnoses.
But for participants whose COVID-19 infections were confirmed with a positive PCR test, “colchicine reduces the risk of the primary end-point, which was the combination of death or hospitalization for COVID-19, by approximately 25 per cent,” which is statistically significant, Tardif told CTV News.
The benefit was most apparent in men over the age of 40 with “at least one risk factor for disease progression,” and who are at higher risk than women for complications arising from COVID-19, said Tardif.
However, McDonald counters that it’s a “barely" positive result.
“You have to treat many people to prevent one hospitalization,” she said -- 70 people would need to take colchicine for 30 days and tolerate "side effects like diarrhea.”
A small number of blood clots were also detected in the group that received colchicine.
The study’s authors did include additional data about the blood clot observations in the peer-reviewed version, but the potential link between the blood clots and the colchicine was not explained.
Instead, Tardif said “this was most likely [by] chance, and... was not a real signal.”
McDonald said to her, that kind of result is also a warning sign.
“I'm a little uncomfortable because the study methodology should have taken care of those chance imbalances,” McDonald said. If one issue comes up by chance, she said, it means there could be other concerns about the study participants and “maybe the randomization wasn't perfect."
She said she would want a study to be able to explain the cause of any adverse effect. If a doctor were to decide to prescribe colchicine for this indication, she advises to be sure that patients give informed consent first.
That’s reflected in the way British Columbia is addressing the issue. It lists colchicine as a possible treatment option after first including it in their pharmaceutical armoury when hospitals were under pressure.
But B.C. guides physicians to “mention the low chance of benefit and the possibility of harm and then together decide whether it's worthwhile," said McDonald.
"It could be worthwhile for some much higher-risk populations -- in particular men, or older people with diabetes, for example."
WILL COLCHICINE BE PRESCRIBED?
The study’s suggestion that doctors consider prescribing colchicine for some patients is also being met with renewed skepticism by those who sit on the province’s drug review committee.
The first time the study raised questions was last January, when Tardif announced preliminary results in a press release and in various interviews, describing colchicine then as "a major scientific discovery" and suggesting that doctors could prescribe right away.
Tardif said this week he “has no regrets" about that decision, because it was the right time “to disclose those results,” during a second wave where people were dying and in hospital and, he said, “where we’re trying to help society."
But scientists around the world criticized the lack of concrete data in the press release. In response, Tardif and his co-authors quickly released a not-yet-peer reviewed manuscript online for everyone to scrutinize.
That still didn’t alleviate many concerns, and it prompted the Institut national d’excellence en sante et services sociaux (INESSS) drug advisory committee to hold a news conference in February explaining they were not recommending colchicine for the time being, given the number of side effects seen in the preprint article -- in particular, a risk of pulmonary embolism or blood clots.
It seems that decision still holds, at least for now. Committee members don’t know yet if they'll need to change their position on colchicine, INESSS spokesperson Olivia Jacques wrote in an email to CTV news.
“The results published yesterday in the Lancet are the same as the previous, only the conclusions are more nuanced," she explained.
She said the committee will analyze the manuscript and will consult with other experts.
One prominent Quebec expert has already weighed in publicly. In an interview with La Presse, Dr. Karl Weiss, Chief of Infectious Diseases at the Jewish General Hospital, said for him “the colchicine file is closed.”
He said he prescribed colchicine at the beginning of the pandemic, when doctors were in a bad way, “but I don’t prescribe it anymore.”
That’s due to Canada’s good fortune and its healthy vaccine supply, reducing the need for treatments at the moment. But the same is certainly not the case for many other countries around the world still being ravaged by COVID-19.
That’s where colchicine might make a difference, Tardif said.
“Certainly there's been a lot of feedback and questions from physicians in India about this," he said.
"We're pleased that the Bill and Melinda Gates Foundation generated a report saying they believe that colchicine is a very interesting addition” in several countries in dire need of medical support, Tardif said.