Little evidence that colchicine benefits COVID-19 patients, Quebec advisory panel finds

Clinical experts with the Quebec government say there isn't enough evidence yet for them to recommend widespread use of colchicine to treat COVID-19 patients, dampening hopes the drugcould be a short-termtool to reduce hospitalizations and deaths.

Last month,the Montreal Heart Institute released a statement vaunting the results of a clinical trial that foundthe rate of hospitalization or death was 21per centlower among patients who tookcolchicine, compared to a placebo. It reported even more impressive results among"patients with a proven diagnosis."

The findings made headlines aroundthe world. Premier Franois Legaultcalled the results "big news."

Colchicine is a cheap, widely available drug in Canada, well-known to doctors for its effectiveness at treating gout. And so far physicians have struggled to findeffective drug treatments for the new disease.

The news release, though, left out key elements of the study. When the researchers released more detailed findings, their peers in the medical community struck a more cautious tone.

McGill'sOffice for Science and Society joined several others in decrying a practise known as"science by press release," whereseemingly exciting findings are published by funding bodies before being peer-reviewed and with little in the way ofdata.

Amid the controversy, the Quebec provincial government's clinical research institute (known by its French initials as the INESSS)quickly undertookitsown detailed analysis of thecolchicinestudy.

In a briefing Thursday with journalists, the INESSSexperts said based on the available evidencethey consider it "premature to support the use of colchicine in non-hospitalized persons with a diagnosis of COVID-19."

Finding inconclusive, INESSS says

The $14-million colchicinestudy, funded in part by the Quebec government,was launched in March, initiallywith the aim of recruiting 6,000 people in six different countries.

Led byDr. Jean-Claude Tardif, director of the Montreal Heart Institute'sresearch centre, the investigatorswanted to see whether the anti-inflammatory medication would limit symptoms of the disease in people with pre-existing medical conditions.

But the study was halted after recruiting4,500 participants. The researchers cited both logistical issues and the desire to get results to health-care professionals as quickly as possible, given the strain the pandemic was placingon hospital resources.

In its review, the INESSS said that was the right decision given the circumstances, and acknowledged Tardif'shypothesis and research design were sound.

Dr. Luc Boileau, the president of the advisory body, said the move to publish the results in a press release, ahead of peer-review, was "not irresponsible but is infrequent."

"We're in the context of a pandemic ... andthere is a legitimate public interest in the results," he said.

But following a close reading of those results, the advisory bodydetermined there was insufficient evidence to draw firm conclusions about the benefits ofcolchicine for COVID-19 patients.

The participants in the study included patients who tested positive via the gold-standard PCR test, as well as those who had been diagnosed simply by virtue of having been exposed to someone with the virus (known as anepidemiological link).

When those two groups were considered together,there was no statistically significantdifference in hospitalizations or deaths between participants receivingcolchicineand those receiving a placebo, said Dr. Michle de Guise, who headed the review.

There was astatistically significantdifference among those who tested positive through PCR. In this smaller group, those who received the drug were 25 per cent less likely to die or require hospitalizations when compared with the placebo group.

Thatwas one of the findings that went into the news release put out by the Montreal Heart Institute. But when considered in absolute terms, the difference is less impressive.

In the placebo group, sixper cent of the2,084 subjects either died or required hospitalization. In the experimental group, 4.6 per cent of2,075subjectsdied or required hospitalization.

From a clinical perspective, that 1.4 percentage pointdifference "means that 71 patients would need to be treated with colchicine to achieve one less event," said de Guise.

Potentially alarming side effect

The study also turned up apotentially frightening side-effect. Eleven participants who tookcolchicineexperienced a pulmonary embolism, compared withtwo in the placebo group.

That alarmed the experts INESSS consulted,de Guise said.

"That was unexpected and it worried them," she added.

The INESSS stressed itsfindings were preliminary and said it would review them asmore data becomes available.

In the meantime, COVID-19 patients interested in using the drug should have a discussion with their physician, saidBoileau.

Quebec's Health Ministry said it would issue guidelines oncolchicinetreatments for COVID-19 after taking the time to analyze the recommendations made by the INESSS.

A spokesperson for theMontreal Heart Institute said Thursday they too would readthe INESSSreport before commenting.