By Patrice Wendling
The oral anti-inflammatory drug may prevent complications and hospitalizations in non-hospitalized patients recently diagnosed with COVID-19, according to one of the researchers in the ColCORONA study.
After one month of treatment, there was a 21% reduction in the risk of the primary composite endpoint of death and hospitalizations that did not reach statistical significance, compared to placebo, in 4,488 outpatients who participated in the global phase 3 study.
However, after excluding 329 patients without a confirmatory polymerase chain reaction (PCR) test, it was reported that the use of colchicine significantly reduces hospitalizations by 25%, the need for mechanical ventilation by 50%, and deaths by 44%.
"We consider this a medical advance. There is no approved treatment to prevent COVID-19 complications in outpatients, to avoid their hospitalization," lead investigator Dr. Jean-Claude Tardif of the Montreal Heart Institute in Quebec, Canada, told Medscape .
"I know that in several countries the data will be analyzed very quickly, and in Greece it was approved on January 24. So that gives hope to patients," he commented.
Following the harm caused by hydroxychloroquine and other proposed drugs, without evidence published in peer-reviewed articles, the response to the announcement was tempered by a desire for more details.
When asked for comment, Dr. Steven E. Nissen of the Cleveland Clinic Foundation in Cleveland, Ohio, was cautious. “The press release about the study is vague and lacks details such as hazard ratios , confidence intervals, and p -values,” he told Medscape.
"It's impossible to evaluate the results of this study without these details. The rigor of the data collection is also questionable," he added. "We'll need to see the manuscript to properly interpret the results."
The data in the press release are difficult to interpret, but early intervention with anti-inflammatory treatment has considerable biological appeal in COVID-19, said Dr. Paul Ridker, a master of public health, who led the pivotal CANTOS study of the anti-inflammatory drug canakinumab in the context of subsequent myocardial infarction and chaired the ACTIV-4B study, which is currently investigating anticoagulants and antithrombotics in outpatients with COVID-19.
"Colchicine is inexpensive and generally well-tolerated, and so far the reported benefits are substantial," Dr. Ridker of Brigham and Women's Hospital in Boston told Medscape . "We're eager to see the full data as soon as possible."
The commonly used antigout and antirheumatic drug costs about 26 cents in Canada and between $4 and $6 in the United States. As previously reported , it reduced time to clinical deterioration and hospital stay but not mortality in the 105-patient GRECCO-19 study (Study of the Effects of Colchicine in the Prevention of Complications of COVID-19).
Dr. Tardif said he hopes to make the data public and that they acted quickly because the evidence was "clinically persuasive" and "the health system is now congested."
“We received the results on Friday, January 22nd at 5 pm, an hour later we were in meetings with our data security watchdog, two hours later we issued a press release, and a day later we were submitting a full manuscript to a major scientific journal; I don’t know if anyone has ever done this so quickly,” he said. “So we’re very proud of what we did.”
ColCORONA was designed to include 6,000 outpatients aged at least 40 years, who were diagnosed with COVID-19 in the last 24 hours and who had at least one high-risk criterion, i.e., minimum age of 70 years, body mass index ≥30 kg/ m2 , diabetes, uncontrolled hypertension , documented respiratory disease, heart failure or coronary artery disease, fever ≥38.4°C in the last 48 hours, dyspnea on seeking medical attention, bicytopenia, pancytopenia, or the combination of a high neutrophil count and a low lymphocyte count.
Participants were randomized to receive either placebo or colchicine at a dose of 0.5 mg twice a day for 3 days and then once a day for another 27 days.
The number needed to prevent one complication of COVID-19 was about 60 patients, Dr. Tardif said.
Colchicine was well tolerated and resulted in fewer serious adverse effects than placebo, he said. Diarrhea occurred more frequently in patients assigned to colchicine, but there was no increase in cases of pneumonia. However, caution should be exercised when treating patients with severe kidney disease.
Tardif said he would not prescribe colchicine to an 18-year-old patient with COVID-19 who did not have any underlying medical conditions, but he would prescribe it to those who met the study protocol.
“As long as it seems to me that a patient is at risk of a complication, I would prescribe it without hesitation,” he said. “I can tell you that when we had the meeting with the data safety watchdog on Friday night, I asked every single board member, ‘If it were you—not that you were treating a patient, but that you had COVID-19 today—would you take it based on the data you’ve seen?’ And every single member of the data safety watchdog said they would.”
"Therefore, we will have the debate in the public domain when the article is published, but I believe that most doctors will use it to treat their patients."
The study was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the US National Institutes of Health; Montreal philanthropist Sophie Desmarais; and the COVID-19 Therapeutics Accelerator supported by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators.