Recurrent Cardiovascular Events Reduced by Anti-Inflammatory Therapy

Canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, could reduce the risk of recurrent cardiovascular events, according to the findings of a recent study.

The randomized, double-blind trial included 10,061 patients who experienced a myocardial infarction prior to the start of the study and had a high-sensitivity C-reactive protein level of 2 mg/L or more. Patients were randomly assigned to receive 50 mg, 150 mg, or 300 mg dosage of canakinumab, which was administered subcutaneously every 3 months, or placebo. The primary efficacy endpoint was defined as nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Hospitalization for unstable angina that led to urgent revascularization was included as the secondary endpoint.
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Patients who received canakinumab experienced greater reductions in high-sensitivity C-reactive protein levels from baseline to 48 weeks after initiating treatment compared with those who received the placebo. Among those who received canakinumab, the median reductions in high sensitivity C-reactive protein levels were 26% greater, 37% greater, and 41% greater than the median reduction among those in the placebo group with 50 mg, 150 mg and 300 mg doses, respectively. However, canakinumab did not lower lipid levels from baseline.

After the median 3.7 years of follow-up, the incidence rate for the primary endpoint was 4.50 events per 100 person-years in the placebo group and 4.11 events per 100 person-years in the 50 mg canakinumab group, 3.86 events per 100 person-years in the 150 mg group, and 3.90 events per 100 person-years in the 300 mg group. Compared with patients in the placebo group, the hazard ratios for the primary endpoint were 0.93 for the 50 mg group, 0.85 for the 150 mg group, and 0.86 for the 300 mg group. However, only the 150 mg dose of canakinumab met the researchers’ prespecificed multiplicity adjusted threshold for statistical significance for the primary and secondary endpoints.

While no significant difference for all-cause mortality was observed between the canakinumab groups and placebo group, canakinumab was associated with higher incidence of fatal infection.

“Anti-inflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering,” the researchers concluded.

—Melissa Weiss

Reference:

Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease [August 27, 2017]. N Engl J Med. doi:10.1056/NEJMoa1707914.