Atherosclerotic Disease Benefits From Interleukin-1β Targeting

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Researchers compared 3 subcutaneous doses of canakinumab in patients who had a previous MI.
Researchers compared 3 subcutaneous doses of canakinumab in patients who had a previous MI.

A regimen of 150 mg canakinumab every 3 months reduced the incidence rate of recurrent cardiovascular events compared with placebo in high-risk patients, according to findings from a double-blind randomized trial published in the New England Journal of Medicine and presented at the 2017 European Society of Cardiology Congress, held August 26-30 in Barcelona, Spain.1,2

In the CANTOS trial (ClinicalTrials.gov identifier: NCT01327846), investigators compared 3 subcutaneous doses of canakinumab (50 mg, 150 mg, and 300 mg), a monoclonal antibody that targets interleukin-1β, with placebo in 10,061 patients who had a previous myocardial infarction.

At baseline, the patient population featured a high-sensitivity C-reactive protein level of ≥2 mg/l. Nonfatal stroke, nonfatal myocardial infarction, or cardiovascular death comprised the primary efficacy end point for this trial.

The groups who received 50 mg, 150 mg, and 300 mg doses of canakinumab experienced a median reduction in the level of high-sensitivity C-reactive protein 26, 37, and 41 percentage points greater than placebo, respectively.

In the placebo group, the incidence rate of the primary end point was 4.50 events per 100 person years at a median follow-up of 3.7 years. The primary end point during the same follow-up period for the medication group was 4.11, 3.86, and 3.90 events per 100-person years in the 50 mg, 150 mg, and 300 mg canakinumab subgroups, respectively. Hazard ratios for the 50 mg, 150 mg, and 300 mg patients compared with placebo were 0.93 (95% CI, 0.80-1.07; P =.30), 0.85 (95% CI, 0.74-0.98; P =.021), and 0.86 (95% CI, 0.75-0.99; P =.031).

Compared with placebo, the use of canakinumab correlated with a higher incidence of fatal infection. With regard to all-cause mortality, no significant differences were observed between the canakinumab and placebo groups (P =.31). The 150-mg dose was the only dose that met the multiplicity-adjusted threshold for statistical significance for both the primary and secondary end points (P =.005). The secondary end point was hospitalization for unstable angina leading to emergency revascularization.

The researchers noted that the effects of 150 mg canakinumab were observed “independent of lipid-level lowering.”

Reference

  1. Ridker PM, Everett BM, Thuren T, et al. Anti-inflammatory therapy with canakinumab for atherosclerotic disease. European Society of Cardiology Congress 2017; August 26-30, 2017; Barcelona, Spain.
  2. Ridker PM, Everett BM, Thuren T, et al. Anti-inflammatory therapy with canakinumab for atherosclerotic disease [published online August 27, 2017]. N Engl J Med. doi:10.1056/NEJMoa1707914
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