Targeting IL-6 in patients at high cardiovascular risk

• Published in: The Lancet (British edition) 2021-05, Vol.397 (10289), p.2025-2027
• Main Authors: Christoffersen, Mette, Tybjaerg-Hansen, Anne
• Format: Article
• Language: English
• Subjects: Albumins; Arteriosclerosis; Atherosclerosis; Biomarkers; Blood pressure; C-reactive protein; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - prevention & control; COVID-19; Creatinine; Cytokines; Epidermal growth factor receptors; Fibrinogen; Health risks; Health services; Heart Disease Risk Factors; Humans; Inflammation; Inflammatory diseases; Innate immunity; Interleukin 6; Kidney diseases; Ligands; Lipids; Lipoproteins; Monoclonal antibodies; Pandemics; Patients; Reduction; Risk Factors; Sensitivity; Signal transduction; Thromboembolism; Thrombosis; Triglycerides
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(21)00985-5

The understanding that atherosclerosis is a chronic inflammatory disorder mediated through both adaptive and innate immunity has led to the hypothesis that anti-cytokine therapies targeting interleukin signalling pathways could serve as adjuncts to lipid lowering in the prevention and treatment of cardiovascular disease.1 The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) showed that targeting interleukin (IL)-1β reduced cardiovascular event rates without lowering lipids or blood pressure.2 The magnitude of this effect was directly associated with the reduction in IL-6 and the downstream clinical biomarker high-sensitivity C-reactive protein (CRP). Secondary endpoints included corresponding changes in fibrinogen and serum amyloid A. Additional biomarker and safety data were collected over 24 weeks of treatment. Because of concerns that the onset of the COVID-19 pandemic might skew the primary inflammation endpoints (potential exogenous cause of high-sensitivity CRP increase), the trial was terminated after 215 patients had completed the first 12 weeks. Future trials of IL-6 inhibition should include other vascular endpoints associated with a proinflammatory response linked to IL-6, such as heart failure, peripheral arterial disease, aortic aneurysm, and arrythmia.10 Caia Image/Science Photo Library AT-H reports consultancies or talks sponsored by Akcea (talks and consultancies on triglycerides and the chylomicronaemia syndrome), AstraZeneca (consultancies on lipid-lowering), Draupnir Bio (consultancies on PCSK9 inhibition), Novartis (coming talks or online teaching on PCSK9 inhibition), Sanofi (talk on lipoprotein[a]), Silence Therapeutics (consultancies on familial hypercholesterolaemia), and Regeneron (consultancies on triglycerides), all outside of the area of work commented on here.