Reduction of major vascular events with IL-1β inhibitor in patients with CKD
Cardiovascular Efficacy of Canakinumab Among Patients with Chronic Kidney Disease: Analyses from the CANTOS Trial
Presented at ACC.18 by Paul Ridker (Boston, MA, USA)Mar. 13, 2018 - news
Introduction and methods
Patients with chronic kidney disease (CKD) have a higher risk of vascular events and all-cause mortality compared to those with normal kidney function. Data suggest that processes related to renal injury and repair results in changes in immunity, including enhanced NLRP3 inflammasome function leading to activation of interleukin-1β (IL-1β). IL-1β is involved in multiple aspects of accelerated atherothrombosis, independent of lipid levels.
The monoclonal antibody canakinumab that targets IL-1β was evaluated in post-MI patients for the reduction of CV events. In the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), stable post-MI patients with hsCRP≥2 mg/mL were randomized to placebo or one of three doses (50, 150, 300 mg) canakinumab. The primary endpoint was a composite of non-fatal MI, non-fatal stroke, and CV death (MACE) and secondary endpoint was MACE plus unstable angina requiring urgent revascularization (MACE+).
In this sub-analysis, the effect of canakinumab on CV events and renal function was evaluated in patients with moderate CKD (eGFR 30-60 mL/min/1.73m2) (n=1875) were compared to those with normal renal function (eGFR >60 mL/min/1.73m2) (n=8184).
- Compared to placebo, MACE+ was reduced with canakinumab treatment in patients with moderate CKD (HR 0.82; 95%CI:0.68-1.00, P=0.05) and in those with normal kidney function (HR 0.86; 95%CI:0.77-0.97, P=0.012)
- Treatment effect on MACE+ was different between CKD patients with on-treatment hsCRP <2 mg/mL (HRadj 0.69; 95%CI:0.54-0.89, P=0.0039) compared to those with on-treatment hsCRP >2 mg/mL (HR adj 0.81; 95%CI:0.64-1.04, P=0.11).
- Treatment effect on CV mortality also differed between those with on-treatment hsCRP<2 mg/mL (HRadj 0.66; 95%CI:0.46-0.94, P=0.0223) and those with on-treatment hsCRP >2 mg/mL (HRadj 0.96; 95%CI:0.68-1.35, P=0.81). Similar findings were seen for total mortality, with on-treatment hsCRP <2 mg/mL showing HRadj 0.76 (95%CI:0.57-1.00, P=0.05) and on-treatment hsCRP >2 mg/mL showing HRadj 0.99 (95%Ci:0.76-1.29, P=0.93).
- Treatment with canakinumab did not result in significant findings for renal function.
Treatment with the IL-1β inhibitor canakinumab resulted in a reduction of CV events in high risk patients with moderate CKD, with a greater reduction in those who achieved on-treatment hsCRP<2 mg/mL compared to those with on-treatment hsCRP>2 mg/mL. It will be interesting to evaluate the efficacy of canakinumab in patients with end-stage renal failure and/or those undergoing dialysis.
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