Canakinumab Does Not Prevent Diabetes Progression, But Reduces MACE in High-Risk Patients

Brendan Everett, MD, MPH

A dyad of analyses presented at the 67^th American College of Cardiology Scientific Sessions in Orlando, Florida, have shown that canakinumab (Ilaris, Novartis) resulted in substantial reductions in major cardiovascular events (MACE) in patients with chronic kidney disease (CKD), and type 2 diabetes, respectively.

However, while the treatment reduces hemoglobin A1C (HbA1c) in patients with pre-diabetes for approximately 9 to 12 months, the effects attenuated over time. According to the results, canakinumab does not prevent the progression from pre-diabetes to diabetes among patients with prior myocardial infarction and high sensitivity C-reactive protein (hsCRP) ≥2 mg/L.

The sub-studies included data from 10,061 patients that experienced myocardial infarction and hsCRP levels of 2 mg/L or more, revealing that the therapy had neither clinically meaningful benefit nor harms to adverse renal events or glucose control.

"Evidence continues to build that inflammation underlies many diseases and health conditions," Brendan Everett, MD, MPH, the director of the General Cardiology Inpatient Service at Brigham and Women’s Hospital, said in a statement. "We find that among heart attack survivors with diabetes or pre-diabetes, canakinumab is effective at reducing the risk of cardiovascular events. Our data also suggest that as cardiovascular disease and diabetes take root, the inflammatory pathways underlying them may diverge."

Everett and colleagues utilized data from the CANTOS trial, which showed the reduction in cardiovascular events in both patients with and without diabetes. When

Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, and colleagues explored the impact of canakinumab in patients with moderate to severe CKD that were at high-risk for developing atherosclerosis. They found that the interleukin-1 inhibitor provided vigorous benefits in reducing MACE, with the highest value granted to those with the most robust anti-inflammatory responses.

In the CANTOS trial, the therapy was tested in 3 doses—50 mg, 150 mg, and 300 mg—administered every 3 months subcutaneously, compared with placebo. At 48 months, levels of hsCRP were 26% higher in the 50-mg dose group, 37% higher in the 150-mg dose, and 41% higher in the 300-mg dose compared to placebo—without lipid level reduction.

Although, only the 150-mg dose met the threshold for clinical significance for both the primary and secondary endpoints (HR, 0.85; 95% CI, 0.74—0.98; P = .021). The secondary endpoint included hospitalization for unstable angina that led to urgent revascularization (HR, 0.83; 95% CI, 0.73—0.95; P =.005)

As the therapy lowers hsCRP, as well as interleukin-6, without a negative effect on lipid levels, it characterizes a new class of atherosclerosis medications, according to Ridker.

"Moving forward, it will be important to extend these data and test the efficacy of canakinumab in patients with end-stage renal failure undergoing dialysis," Ridker said. "In that setting, hsCRP is a powerful predictor of risk while LDL-C is not, and dialysis is one of the only settings where LDL reduction has not been highly effective."

Everett and colleagues’ findings were published simultaneously in the Journal of the American College of Cardiology, while the findings from Ridker and colleagues are impending.

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