Canakinumab is a therapeutic monoclonal antibody targeting interleukin-1β. The trial randomly assigned patients with a previous myocardial infarction and an elevated level of high-sensitivity C-reactive protein to receive one of three doses of canakinumab (50-mg, 150-mg or 300-mg) or placebo. As compared with placebo, canakinumab reduced the high-sensitivity C-reactive protein level from baseline in a dose-dependent fashion by 3 months and sustained it throughout the dosing period, with no reduction in the LDL cholesterol level.
The hazard ratios for the primary endpoint as compared with placebo were as follows: in the 50-mg group, 0.93 (95% CI 0.80-1.07; P=0.30); in the 150-mg group, 0.85 (0.74-0.98; P=0.021); and in the 300-mg group, 0.86 (0.75-0.99; P=0.031).
Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (HR for all canakinumab doses vs. placebo, 0.94; 0.83 to 1.06; P=0.31).
In a related editorial, the author discusses the significance of these findings, stating that “Despite the scientific and clinical excitement associated with having a new mechanism of action to attack in the treatment of coronary artery disease, a better understanding of the risks and benefits of this form of therapy is needed. Given that there was no observed effect on cardiovascular mortality in this trial, more information about the details of the myocardial infarctions is needed to better assess the clinical benefit of canakinumab. We also need additional information about the fatal infections encountered in CANTOS. Furthermore, any discussion of the use of canakinumab in patients with a previous myocardial infarction must consider cost. Given monthly for approved indications, canakinumab is priced at approximately $200,000 per year in the United States. Such pricing may be suitable for rare diseases, but not for a common indication such as coronary artery disease, even if given every 3 months. CANTOS has helped move the inflammatory hypothesis of coronary artery disease forward scientifically. However, the modest absolute clinical benefit of canakinumab cannot justify its routine use in patients with previous myocardial infarction until we understand more about the efficacy and safety trade-offs and unless a price restructuring and formal cost-effectiveness evaluation supports it.”
A separate analysis evaluating the effect of canakinumab on incident lung cancer in patients with atherosclerosis has been published in the Lancet.