Colchicine Cost-effective in Canada, and Even in the US: COLCOT

Low-dose colchicine not only lowers the risk of ischemic CV events post-MI, it also can do so cost-effectively, according to the latest numbers from COLCOT.

This is true from the perspective of the Canadian single-payer healthcare system, the new report’s main focus, as well as when viewed from the US Medicare and private insurer vantage points, Michelle Samuel, PhD (Montreal Heart Institute, Canada), reported during today’s virtual American College of Cardiology (ACC) 2020 Scientific Session.

The randomized trial’s results—which last year renewed interest in the inflammatory hypothesis of CVD—drew headlines when they were presented at the 2019 American Heart Association meeting and published in the New England Journal of Medicine.

Colchicine, an anti-inflammatory drug indicated for gout and pericarditis, is available for pennies in much of the world. But for US consumers, cost is a concern thanks to a complicated regulatory history that involves belated branding, unexpected price hikes, and limited generic availability.

Colchicine costs 26 cents per pill in Canada, as compared to $4 to $6 in the United States, Samuel noted.

“We talk a lot in the cardiovascular community about drugs that are both effective and that we can afford to pay for. And these data are obviously exceptional in that regard,” said Paul Ridker, MD (Brigham and Women’s Hospital, Boston, MA), discussing the findings online during ACC 2020’s virtual broadcast.

We’ve all come to recognize that residual inflammatory risk is another very large part of the equation that we deal with. Paul Ridker

Ridker led CANTOS, which in 2017 raised hopes for an anti-inflammatory approach to preventing CV events, as well as CIRT, which subsequently dashed them in late 2018. “As an investigator in the inflammation biology field for the last 35 years,” he said, it’s important to realize that although much of the focus is currently on the residual risk posed by cholesterol, “we’ve all come to recognize that residual inflammatory risk is another very large part of the equation that we deal with.”

What’s particularly noteworthy here is that colchicine comes at a low cost, as compared to the pricey monoclonal antibody explored in the proof-of-concept CANTOS trial, Ridker observed. With colchicine being dominant over placebo in these COLCOT analyses, “it means you save money. I think that’s the message you’re getting here,” he said.

An Eye Toward Cost

In COLCOT, investigators randomized 4,745 patients (mean age 60.6 years; 19.2% women) in 12 countries to colchicine (0.5 mg once daily) or placebo. Mean time of enrollment was 13.5 days post-MI, and 93% of participants had undergone PCI.

Over a median follow-up of 22.6 months, patients in the colchicine group were less likely to experience a primary efficacy endpoint (death from CV causes, resuscitated cardiac arrest, MI, stroke, or urgent rehospitalization for angina leading to revascularization) than those given placebo—5.5% versus 7.1% (HR 0.77; 95% CI 0.61-0.96).

Samuel explained that the new analysis modelled the cost-effectiveness of colchicine during the trial period and over a 20-year lifetime. Events entered into the Markov model included components of the primary endpoint, non-CV-related death, and pneumonia, the only serious adverse event found to be significantly different between the colchicine and placebo groups (0.9% vs 0.4%; P = 0.03). Both first and second events were included.

In Canada, addition of low-dose colchicine to standard-of-care therapy post-MI is the economically dominate strategy, reducing mean overall per-patient costs by 47% in the in-trial period ($265 vs $502) and 69% in the lifetime period ($2,590 vs $8,239 with placebo). These advantages held up across multiple sensitivity analyses.

Average number of quality-adjusted life years (QALYs) gained was higher with colchicine than with placebo, both during the trial (1.34 vs 1.30) and over the 20-year lifetime (11.68 vs 8.82).

From the Canadian perspective, colchicine’s incremental cost-effectiveness ratio (ICER) dominance was maintained up to a cost of 55 cents per pill. “And colchicine was cost-effective at a $50,000 willingness to pay threshold of about $3.50,” Samuel said. For the 20-year lifetime, “dominance was maintained until about $1.25 per pill, and it was cost-effective up and through $4.”

The researchers repeated their math for the US healthcare landscape. Over a 20-year lifetime, colchicine was economically dominant at $5 or less and cost-effective at $6 in the Medicare system; with private insurance, colchicine held the lead all the way up to $6.

What’s Next

Looking ahead, Ridker said, these results must be replicated. If they are, “that will be very easy for guideline committees to say, ‘Hey, here’s a therapy that clearly approaches the inflammatory cascade that’s very, very cost-effective,’ and this might become the statins of the anti-inflammatory world, which I think would be just terrific,” he commented, pointing out that data from LoDoCo2 and CLEAR-SYNERGY are on the way.

Ridker asked Samuel about where the COLCOT team is headed next. “We are planning to do a high-risk primary prevention trial in type 2 diabetes. Hopefully after all this [COVID-19] crisis, we can get that started,” she replied.

Also in the discussion, panelist Jennifer Robinson, MD (University of Iowa, Iowa City), highlighted a widely accepted cost-saving therapy that already exists: statins.

“Let’s not forget those, because I think the point really needs to be made again that all of these trials we are talking about are occurring in the background of optimal medical therapy, [with many patients] on high-intensity or at least moderate-intensity statins,” she emphasized. New options, Robinson argued, must be considered on this backdrop.