Canakinumab and cardiovascular outcomes: results of the CANTOS trial

Abstract

IL-1 cytokines are mainly responsible for controlling a series of pro-inflammatory reactions induced in response to pathogen mediated tissue injury. Among the IL-1 cytokine family, IL-1 β results in upregulation of genes responsible for boosting immune system reactivity and inflammatory response. With growing pathophysiological relevance of IL-1β in a myriad of disease pathogenesis, new biological drugs have been developed in recent years. One such drug, Canakinumab, targeting IL-1β has been recently approved for clinical use. The recent results from the CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcome Study) trial are encouraging in this aspect. The results suggest that anti-inflammatory therapy using canakinumab at a dose of 150 mg every 3 months led to significantly lower recurrent cardiovascular events than the placebo drug. These results were independent of lipid-lowering effects of these drugs. If the results are widely applicable, the CANTOS trial would reaffirm the hypothesis of atherothrombosis due to inflammation, hence supporting the need for a cytokine-based therapy for the secondary prevention of cardiovascular diseases. Moreover, the potential benefits of the phenomenal reduction in the inflammatory cascade induced by canakinumab should be carefully balanced against its long-term safety profile which is yet unknown. However, the inflammatory hypothesis of atherothrombosis supports a cytokine-based therapy for the secondary prevention of cardiovascular disease. Furthermore, the potential benefits from the reduction in inflammatory markers induced by canakinumab should be carefully balanced against its unknown long-term safety profile.

Activation of 5-HT2 Receptors Reduces Inflammation in Vascular Tissue and Cholesterol Levels in High-Fat Diet-Fed Apolipoprotein E Knockout Mice

“…A recent study has found that cytokine-based/anti-inflammatory therapy may be more efficacious in preventing cardiovascular disease than cholesterol-lowering compounds 42 . Results from the CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcome Study) trial show that the IL-1β inhibitor canakunumab, independent of lipid-lowering, significantly reduces the risk of cardiovascular disease and recurrent cardiovascular events in patients with previously diagnosed myocardial infarction 43 .…”

Effects of tumour necrosis factor on cardiovascular disease and cancer: A two-sample Mendelian randomization study

“…Importantly, targeting inflammation using the biological therapy has previously been successful. Canakinumab, which neutralizes IL1B, reduced recurrent cardiovascular outcomes in patients with a high inflammatory burden in a clinical trial even though the results of this trial were substantially lower than expected [29]. The underlying mechanism for TNF-driven atherothrombosis could be via a variety of proposed mechanisms, including favourable effects on circul1ating lipids, insulin resistance, endothelial dysfunction, leucocyte recruitment, oxidative stress, vasodilation or coagulation [30].…”

The microbiome and cytosolic innate immune receptors

“…This large phase 3 clinical trial aimed at studying the cardiovascular outcomes of canakinumab‐mediated IL‐1β blockade. The trial showed that IL‐1β neutralization reduced the incidence of cardiovascular disease 224 . However, it did not reduce the incidence of new‐onset diabetes mellitus, 225 highlighting that pathophysiological conclusions drawn from preclinical research are in some instances too simplistic, and may neglect the more nuanced aspects of innate immune sensor regulation and simultaneous contributions of various immune components.…”