From clinical observations to molecular mechanisms and back to patients: the successful circuit of the CANTOS study

Atherosclerosis, a leading cause of death worldwide, manifests as a chronic disease of the arterial wall, characterized by a complex etiology. Decades of experimental studies and clinical evidence depicted a scheme of atherogenesis that clearly highlights the involvement of all the cell types composing vessel walls, interacting with infiltrating inflammatory cells. Many other risks factors, like hypertension, diabetes, cholesterol levels and cigarette smoking, impact on atherogenesis, making things even more complex. On this notice, a variety of therapeutic and prevention strategies were able to reduce the risk deriving from the above mentioned factors, contributing to a significant part of the successes obtained in cardiovascular medicine. The CANTOS trial was conceived to test the hypothesis that inflammation and immune activation are pathogenetic events in the atherosclerotic disease and not simply bystander processes related to vascular tissue damage. Designed as a double-blinded randomized trial for secondary prevention of cardiovascular events, CANTOS enrolled 10 061 patients with prior myocardial infarction and elevated levels of high sensitivity Creactive protein (hsCRP), equal or higher than 2 mg/L. Randomized in four groups receiving canakinumab, a human monoclonal antibody neutralizing interleukin-1 b (IL-1b ), at three different dosages (50, 150 and 300 mg, administered subcutaneously every 3 months) or placebo, on top of their standard therapy. Accordingly to the trial’s strategy, canakinumab Prof. Giuseppe Lembo MD PhD graduated from Federico II University of Naples, Italy. After receiving PhD and habilitation as clinical specialist in cardiovascular medicine, he worked for two years as a visiting fellow at University of California at San Diego, in the Department of Medicine and Center for Molecular Genetics. From 1995, he coordinated research and clinical activity of the Department of Angiocardioneurology and Translational Medicine at IRCCS Neuromed (Pozzilli-IS, Italy). He was appointed Associate Professor of Internal Medicine at Sapienza University of Rome in 2000. From 2006, he is serving as Professor of Medical Science and Applied Techniques in the same University, leading the Clinical and Research Department of Angiocardioneurology and Translational Medicine based at IRCCS Neuromed. Prof. GL is member of national and international academic societies for hypertension and cardiovascular diseases, advisory scientist for the Italian Ministry of Health and Italian Ministry of Research and Education. His research activity started in the 1980s with studies on the pathophysiological role of autonomic nervous system in hypertensive patients, and evolved in the investigation of molecular mechanisms of hypertension in experimental models. Prof. GL’s work focused on the dissection of adaptive and maladaptive processes involved in cardiac remodeling to pressure overload, of molecular mechanisms responsible for vascular injury in hypertension, and more recently on the role of neural modulation of immunity in the onset of hypertension. Overall his research activity led to the publication of numerous papers on high impact journals, as Cell, Nat Med, Immunity, Nat Commun, J Clin Invest, J Exp Med, Circulation, Cardiovasc Research, etc. His research has been supported by national and international granting agencies. He has been serving and is still currently involved as Principal Investigator of his Clinical Center in multicentric international clinical trials.