AN The press release from a Canadian research group increased hope that treating people newly diagnosed with Covid-19 with colchicine, a drug commonly used to treat gout, could reduce the risk that they will need to be hospitalized.
But outside experts said the data provided is too limited to draw conclusions, leading to discussions about the risks of conducting science through press releases, rather than more detailed manuscripts in peer-reviewed journals. Everyone expected colchicine, a cheap, globally available generic drug with controllable side effects, to prove beneficial.
“I don’t say, ‘Oh, I don’t believe it,'” said Ashish Jha, dean of Brown University School of Public Health. “It is possible. There is a lot of plausibility here. This could be a real discovery and, if it is, it would be great. But this press release doesn’t get us there.”
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In the statement, which was released on Friday, the Montreal Heart Institute said the rate of hospitalization or death was 21% lower among patients in their COLCORONA study who received colchicine compared with those who were randomly assigned to receive a placebo. The study involved 4,488 patients.
But here’s a caveat: the press release said that these results were not statistically significant, although the numbers are close. When the researchers excluded 329 patients who were diagnosed with Covid-19 based on family contacts or clinical symptoms, but who had no positive CRP tests, there was a 25% reduction in hospitalization and substantial reductions in the need for mechanical ventilation and deaths.
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External experts consider these results less reliable because the study did not achieve its main objective. They also agreed that the number of patients who needed mechanical ventilation or who died is likely to be small, making it difficult to draw firm conclusions. The press release does not include absolute figures on the number of people who were hospitalized, needed ventilators or died.
“No one is going to jump to conclusions when someone says something is close to statistical significance and you can’t see the data,” said Craig Spencer, director of Global Health in Emergency Medicine at the New York Presbyterian Medical Center / Columbia University. it would be huge, it would be wonderful, but I need more – we all need a little more. “
The history of seemingly promising drugs that failed, including, most famously, the hydroxychloroquine malaria drug, left many researchers cautious.
“How many therapies seemed to have promising first-line results and look what happened?” said Ethan Weiss, a cardiologist at the University of California, San Francisco. He gave the example of remdesivir, made by Gilead, where the test results are seen as conflicting. “Let’s see what the real results look like and then we can talk.”
In 2019, the same researchers from the Montreal Heart Institute published a study showing that colchicine, which supposedly suppresses inflammation and the immune response, may benefit patients who have had heart attacks, in part by preventing returning visits to the hospital. These results were published in the New England Journal of Medicine. The researchers began their Covid-19 study on colchicine in March, when the pandemic was beginning to hit North America heavily.
Jean-Claude Tardif, the lead investigator for the 2019 and current study, said his team felt it was important to disseminate the results quickly, but that they would publish them in a medical journal and also felt it was important to get most of the data out. of the press release.
The press release calls the results “clinically persuasive” and Tardif is quoted as saying that colchicine is “the first oral drug in the world whose use can have a significant impact on public health and potentially prevent Covid-19 complications for millions of patients. ”.
Tardif said he was in a hurry – he does not expect to sleep this weekend – to prepare a report with the complete data for a medical journal. It is not clear why there was a need to anticipate the publication of the journal with a release that did not include clear numbers. This is more likely to be done by pharmaceutical companies, which have a duty to inform investors about events that can move the market.
The COLCORONA study was funded by governments and philanthropic entities, including the Quebec government; the US National Heart, Lung and Blood Institute; philanthropist Sophie Desmarais; and the Covid-19 Therapeutics Accelerator, launched by the Bill & Melinda Gates Foundation, Wellcome and Mastercard, so there was no obligation to report the results immediately.
The results were also less detailed than those of some other press releases during the pandemic, including the result of the RECOVERY study, which showed efficacy against Covid-19 of another inexpensive drug, dexamethasone. This press release included detailed statistical information and the findings were published in the New England Journal a month later.
“The result is credible, but it is so vague – and we don’t have many details – that it is very difficult to know how to interpret it,” said Steven Nissen, cardiologist and clinical researcher at the Cleveland Clinic.
Nahid Bhadelia, an infectious disease physician at Boston University, also said he needed to see the data – and that he doesn’t like science in a press release. But she was optimistic. “I think it makes sense,” she said. “We need to see the data, but it fits the scenario that SARS-CoV-2 leads to some type of innate immunity dysfunction.”
The study, originally scheduled to run until March 2021, was designed to enroll 6,000 volunteer patients who had not been hospitalized who would be randomly assigned to receive half a milligram of colchicine twice daily for three days, followed by a once daily dose. or a placebo for 27 days. Neither the researchers nor the patients knew which group the patient was in. The patients were recently diagnosed and had not been hospitalized, an earlier stage of the disease than most other studies. All were over 40 and each had at least one risk factor for developing severe Covid-19.
It is possible to make reasoned assumptions about the results. Tardif said that about 5% of patients were hospitalized. The results with 225 or 250 hospitalized patients – meaning that about 30 hospitalizations have been avoided – generally seem to agree with the results described in the statement. David Boulware of the University of Minnesota, an infectious disease medical scientist, called this “a significant step forward, but not a leap.”
Eric Topol of the Scripps Research Translational Institute sent me an email that, although “many data points are missing”, the potential for early therapy would be “welcome” because the only similar therapies are monoclonal antibodies that must be administered intravenously and “are at fault still not getting used to it.”
The decision to stop the study earlier than expected was made, Tardif said, because waiting would mean waiting months before the drug could be useful to patients now. He said that when the data security and monitoring board, a panel of outside experts who monitor the study, met Friday night, he asked if they thought the results were convincing and whether they would advise a patient or member of the family diagnosed with Covid-19 to take colchicine. Everyone said yes.
That story was confirmed by Marc Pfeffer, the Dzau professor of medicine at Harvard Medical School, who is a member of the study’s data security and monitoring board. Pfeffer said he was convinced that colchicine was safe, although it had side effects. In the NEJM report on its usefulness for people with heart disease, those taking colchicine were more likely to have diarrhea and develop pneumonia.
Pfeffer praised Tardif’s group for being able to conduct a large randomized trial in patients who have not been hospitalized, something others have struggled to do. He said that, over the results, the data was convincing.
“I think the results are clinically convincing and I’m sorry that you don’t have the results to see that,” said Pfeffer. “But you will be going soon.”
There are also other studies testing colchicine, including an arm from the RECOVERY study, which is evaluating the drug in sicker patients.