358Understanding and mitigating the risk of infection with canakinumab

Abstract

Innate immunity drives atherogenesis and cardiovascular risk, but also participates in host defenses against pathogens. The Canakinumab Anti-Inflammatory Thrombosis Outcomes Trial (CANTOS) showed that treatment with the antiinterleukin- 1β antibody canakinumab improved cardiovascular outcomes, but associated with a small increase in fatal infections (Table). To inform measures to minimize infections, we analyzed CANTOS data to ascertain 1) who is at risk for developing infections and 2) what types of infections associate with canakinumab treatment. The study evaluated the three doses of canakinumab vs. placebo in 10,066 patients over a median of 3.5 years (32663 patient-years, Table). The incidence of infections showed stability over time. Risk factors for infections in canakinumab-treated patients included age and chronic kidney disease. The most commonly reported serious infections included sepsis, cellulitis, and pneumonia. Cellulitis and pneumonia were more frequent in patients with diabetes and asthma/chronic obstructive lung disease. There was no excess of opportunistic infections or of tuberculosis (Tb) with canakinumab treatment. To help manage the slight excess risk for infections with canakinumab treatment, these results suggest characteristics of patients who merit heightened awareness of infections when treated with canakinumab, and warrant consideration of early institution of antimicrobial therapy for suspected bacterial infections. In CANTOS, the substantial drop in cancer mortality balanced the increase in infectious deaths due to this anti-inflammatory intervention.