title: Use and role of monoclonal antibodies and other biologics in preventive cardiology.
abstract: Biotechnological advances now enable the design of fully human antibodies to target specific antigens in a growing number of diseases. Monoclonal antibodies (mAbs) differ from traditional small chemical molecules in several ways: (1) biological production ‒ they are grown in and extracted from cell cultures; (2) specificity ‒ they demonstrate high target specificity, with a low risk of drug-drug interactions; (3) administration ‒ they are delivered parenterally (intravenously or subcutaneously); (4) dosage interval ‒ their extended half-lives generally allow for spaced dosing (from weekly to monthly). In cardiology, fully human mAbs directed against proprotein convertase subtilisin / kexin type 9 (PCSK9) have shown to be effective in reducing low-density lipoprotein cholesterol (LDL-C) in phase II clinical trials among patients with familial hypercholesterolaemia (FH). PCSK9 inhibitors have just received approval for the treatment of FH and clinical atherosclerotic disease, and patients not at target under maximally tolerated statin therapy or intolerant to statins. Large-scale phase III trials are currently assessing the role of PCSK9 inhibitors in the secondary prevention setting for patients with acute coronary syndromes (ACS) and poorly controlled LDL-C under evidence-based therapies. Another area currently under investigation for fully human mAbs in secondary prevention is their potential ability to inhibit inflammatory pathways. In this context, canakinumab, a specific mAb inhibiting interleukin-1β (IL-1β), has already received approval for the treatment of systemic juvenile idiopathic arthritis. The canakinumab anti-inflammatory thrombosis outcomes trial (CANTOS) is an ongoing trial assessing whether inhibition of IL-1β could reduce the occurrence of cardiovascular adverse events in 17,200 patients with ACS and with defined persisting inflammation.
authors.affiliation: Cardiology Division, Geneva University Hospitals, Switzerland.
authors.forename: Baris
authors.initials: B
authors.lastname: Gencer
authors.affiliation: Tampere University Hospital, Finland.
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
authors.affiliation: Prism Scientific SarL, Switzerland.
authors.forename: Aliki
authors.initials: A
authors.lastname: Buhayer
authors.affiliation: Cardiology Division, Geneva University Hospitals, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Mach
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000517:prevention & control; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001171:Arthritis, Juvenile / Q000188:drug therapy; D050197:Atherosclerosis / Q000188:drug therapy; D001688:Biological Products / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000187:drug effects; D002986:Clinical Trials as Topic; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy; D051379:Mice; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D055502:Secondary Prevention / Q000379:methods*; D012697:Serine Endopeptidases / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001688:Biological Products; D008078:Cholesterol, LDL; C541220:canakinumab; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases