In the 150 mg group, the P values for both hazard ratios met the prespecified multiplicity-adjusted thresholds for statistical significance. Although the hazard ratios were similar in the 300 mg group and in the placebo group, the prespecified thresholds for significance were not met in that case. Still, “both a pooled analysis of all canakinumab doses and a trend analysis suggested a beneficial effect of canakinumab with regard to cardiovascular outcomes,” the researchers concluded.
Consistent with the known effects of interleukin-1β inhibition, canakinumab also resulted in significantly fewer reports of arthritis, gout, and osteoarthritis than did the placebo group. Although significantly more deaths were attributed to infection or sepsis in the pooled canakinumab groups than in the placebo groups, cancer mortality was found to be significantly lower with canakinumab than with placebo.
The results of this study suggest that reducing vascular inflammation may significantly lower the incidence of recurrent cardiovascular events. Inhibition of interleukin-1β represents only one of many potential anti-inflammatory pathways that might serve as targets for atheroprotection.
“Our data suggests that other antiinflammatory interventions, such as those that directly inhibit NLRP3 function or that alter downstream interleukin-6 signaling, may also be beneficial in reducing cardiovascular risk,” the researchers observed.
The lowered cancer risk among patients assigned to receive canakinumab is consistent with experimental data that relate interleukin-1 to the progression and invasiveness of certain tumors, particularly lung cancer. This finding may present another promising lead for future research.
Ridker PM, Everett BM, Thuren T, et al. “Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.” N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914. [Epub ahead of print]