title: Canakinumab for the treatment of cryopyrin-associated periodic syndromes.
abstract: Familial cold-induced autoinflammatory syndrome, Muckle-Wells syndrome and neonatal-onset multisystem inflammatory disease make up cryopyrin-associated periodic syndromes (CAPS). These are autoinflammatory inherited disorders caused by autosomal dominant gain-of-function mutations in the NLRP3 gene, located on chromosome 1q44. Cryopyrin/NALP3/NLRP3 is an essential component of intracellular inflammasomes that activate caspase-1, which in turn converts interleukin-1beta (IL-1beta) to its active form. IL-1beta is a potent cytokine that activates diverse elements of the immune and inflammatory systems leading to the pathogenic changes characteristic of CAPS. There is therefore much interest in the development of IL-1beta blocking agents as novel biologic treatments for these conditions. Canakinumab (ACZ-885; Ilaris, Novartis Pharma) is a fully humanized monoclonal antibody (mAb) specific for IL-1beta and is indicated for a wide range of inflammatory disorders including CAPS. This review will assess the utility of canakinumab as a treatment for CAPS.
authors.affiliation: Division of Applied Medicine, Institute of Medical Science, University of Aberdeen, Foresterhill, Aberdeen, UK. g.m.walsh@abdn.ac.uk
authors.forename: Garry M
authors.initials: GM
authors.lastname: Walsh
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002352:Carrier Proteins / Q000235:genetics; D002986:Clinical Trials as Topic; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000502:physiology; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C541220:canakinumab