Introduction: The widespread prevalence of cardiovascular disease (CVD) and its impact on morbidity and mortality requires effective secondary prevention measures. For years, inflammation has been advocated as a key mediator of atherosclerosis and its associated complications. Drugs for secondary prevention of CVD events include interventions aimed at risk factors control and antithrombotic management, but there is no drug currently recommended that specifically targets inflammation. Recently, the inflammatory hypothesis of atherosclerosis has been confirmed by a randomized clinical trial of canakinumab, a monoclonal antibody that blocks an inflammatory pathway mediated by interleukin-1β. Areas covered: This article reviews the pharmacology of canakinumab, its current clinical development status and upcoming regulatory perspectives. Expert opinion: In the CANTOS trial, canakinumab 150 mg met the pre-specified criteria of statistical significance, showing a reduction in combined cardiovascular events, myocardial infarction, re-hospitalization due to urgent revascularization and any coronary revascularization, but no impact on all-cause or cardiovascular death. There were more death attributed to sepsis or infection with canakinumab than placebo, but fewer reports of arthritis, gout, osteaoarthritis and cancer-related death. Because interleukin-1β is only one of the potential pro-inflammatory pathways that may serve as a target for atherothrombotic protection, other anti-inflammatory drugs may be the object of future investigations. If approved, the initial penetration of canakinumab will face hurdles in view of cost issues, but costs are likely to decrease if the drug loses its present status of orphan drug with the new indication.

Canakinumab for secondary prevention of atherosclerotic disease

Capodanno, Davide;
2017-01-01

Abstract

Introduction: The widespread prevalence of cardiovascular disease (CVD) and its impact on morbidity and mortality requires effective secondary prevention measures. For years, inflammation has been advocated as a key mediator of atherosclerosis and its associated complications. Drugs for secondary prevention of CVD events include interventions aimed at risk factors control and antithrombotic management, but there is no drug currently recommended that specifically targets inflammation. Recently, the inflammatory hypothesis of atherosclerosis has been confirmed by a randomized clinical trial of canakinumab, a monoclonal antibody that blocks an inflammatory pathway mediated by interleukin-1β. Areas covered: This article reviews the pharmacology of canakinumab, its current clinical development status and upcoming regulatory perspectives. Expert opinion: In the CANTOS trial, canakinumab 150 mg met the pre-specified criteria of statistical significance, showing a reduction in combined cardiovascular events, myocardial infarction, re-hospitalization due to urgent revascularization and any coronary revascularization, but no impact on all-cause or cardiovascular death. There were more death attributed to sepsis or infection with canakinumab than placebo, but fewer reports of arthritis, gout, osteaoarthritis and cancer-related death. Because interleukin-1β is only one of the potential pro-inflammatory pathways that may serve as a target for atherothrombotic protection, other anti-inflammatory drugs may be the object of future investigations. If approved, the initial penetration of canakinumab will face hurdles in view of cost issues, but costs are likely to decrease if the drug loses its present status of orphan drug with the new indication.
2017
Canakinumab; inflammation; interleukin-1β; Pharmacology; Drug Discovery3003 Pharmaceutical Science; Clinical Biochemistry
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/315105
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