C-Reactive Protein Response to a Single Canakinumab Dose Predicts Long-Term Benefit

Inflammation has long been hypothesized to play a causal role in the pathogenesis of atherosclerosis, and results from the industry-funded, randomized, placebo-controlled CANTOS trial — which studied canakinumab, a monoclonal antibody targeting interleukin-1β — supported this hypothesis. In this study of about 10,000 patients with previous myocardial infarction, canakinumab (500 mg) given subcutaneously once every 3 months reduced the rate of a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death (hazard ratio, 0.85) at 4-year follow-up (NEJM JW Cardiol Oct 2017 and N Engl J Med 2017; 377:1119). To assess the relationship between on-treatment concentrations of high-sensitivity C-reactive protein (hsCRP) and later outcomes, researchers performed a prespecified secondary analysis of the study results.

Participants randomized to canakinumab who achieved hsCRP concentrations <2 mg/L had, 4 years later, a 25% reduction in major adverse cardiovascular events (multivariable adjusted HR, 0.75) and reductions in cardiovascular and all-cause mortality (AHR for each, 0.69). In contrast, canakinumab participants whose hsCRP levels continued to be ≥2 mg/L showed no significant improvement in adverse cardiovascular events or cardiovascular or total mortality.