[MK TEST DO NOT TOUCH] Canakinumab keeps adverse cardiac events at bay

Among patients with a history of myocardial infarction (MI) and elevated levels of high-sensitivity C-reactive protein (hsCRP), canakinumab effectively prevents the occurrence of adverse cardiac events over nearly 4 years, according to results of the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS), as presented in the recently concluded American College of Cardiology Annual Scientific Session (ACC 2022).

CANTOS enrolled 10,061 patients (mean age 61 years, 26 percent women) who were randomly assigned to receive 50- (n=2,170), 150- (n=2,284), or 300-mg (n=2,263) doses of canakinumab, or placebo (n=3,344). Canakinumab was administered subcutaneously once every 3 months. Only those who had a history of MI and had hsCRP levels ≥2 mg/L were eligible.

At baseline, 40 percent of patients had diabetes while the median low-density lipoprotein cholesterol level was 82 mg/dL. Over a median follow-up of 3.7 years, the composite incidence of cardiovascular death, MI, or stroke, the study’s primary outcome, occurred at rates of 4.11, 3.86, and 3.90 per 100 person-years in the 50-, 150-, and 300-mg dose groups, respectively. [Ridker PM, et al, ACC 2022]

Meanwhile, such an endpoint occurred at an incidence rate of 4.50 per 100 person-years in the placebo arm. Of all active treatment groups, only the 150-mg canakinumab dose resulted in a statistically significant difference relative to placebo (p=0.02).

However, when looking at total cardiovascular events, comprised of the primary composite endpoint with coronary revascularization, the researchers observed a significant benefit of canakinumab over placebo.

Total cardiovascular events occurred at a rate of 8.4, 8.3, and 8.2 per 100 person-years in the 50-, 150-, and 300-mg dose groups, respectively, all significantly lower than that in the placebo arm (10.4 per 100 person-years; p=0.004, p=0.002, and p=0.001, respectively).

Such a reduction in the primary outcome remained the same in patients with diabetes (hazard ratio [HR], 0.85, 95 percent confidence interval [CI], 0.70–1.03), pre-diabetes (HR, 0.86, 95 percent CI, 0.70–1.06), and normoglycaemia (HR, 0.81, 95 percent CI, 0.49–1.35).

Moreover, all active treatment groups saw significant reductions in hsCRP from baseline relative to placebo. The 50-mg dose, for instance, induced 26-percent greater drop in hsCRP vs placebo; corresponding values were 37 percent and 41 percent for the 150- and 300-mg dose groups (p<0.001 for all).

In terms of safety, the researchers noted that incident diabetes occurred at comparable rates across all treatment arms (log-rank p=0.84). However, fatal infections or sepsis were nearly twice as common in the combined canakinumab group vs placebo group (0.31 vs 0.18 per 100 person-years; p=0.02). Such an effect occurred even after explicitly excluding patients with chronic or recurrent infections during trial enrollment.

“Among patients with a history of MI and elevated hsCRP, canakinumab was effective at preventing adverse cardiac events over a median of 3.7 years,” the researchers said. “The amount of hsCRP reduction from canakinumab might provide a mechanism for predicting the clinical response from this medication.”