title: Efficacy and safety of canakinumab in cryopyrin-associated periodic syndromes: results from a Spanish cohort.
abstract: OBJECTIVE
  Cryopyrin-associated periodic syndromes (CAPS) are dominantly-inherited autoinflammatory diseases. The uncontrolled IL-1β overproduction observed in these patients is the rational basis to treat them with anti-IL-1 drugs. The objective of this study was to evaluate the efficacy and safety of treatment with the long-lasting fully humanised anti-IL-1β monoclonal antibody canakinumab in a Spanish cohort of patients with CAPS.
  
  
  METHODS
  Clinical and laboratory data of CAPS patients carrying a heterozygous germline NLRP3 mutation were obtained. The initial treatment scheme with canakinumab was 150 mg/8 weeks administered subcutaneously in adult patients and 2 mg/kg/8 weeks in paediatric patients.
  
  
  RESULTS
  Eight unrelated patients were enrolled. Canakinumab was the first anti-IL-1 drug used in three of them; five were already receiving anakinra. The clinical response to the initial canakinumab scheme was positive in all patients, and was quickly observed in the first 24-72 hours. Four required increasing the frequency and/or dose of canakinumab. A limited or no efficacy in those symptoms related to consequence of the deforming arthropathy and neurosensorial deafness was observed. The adverse side effects were restricted to infectious complications in a small percentage of patients. The treatment was well tolerated by all patients, with no reactions at drug site injections.
  
  
  CONCLUSIONS
  Canakinumab caused fast and sustained remissions in most clinical and biochemical manifestations in all enrolled patients, with a limited efficacy in the structural lesions. Dose adjustments seem to be necessary for children and/or for patients with the most severe CAPS phenotypes. Treatment was well tolerated with a low incidence of adverse effects.
authors.affiliation: Paediatric Rheumatology Unit, Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues, Spain. janton@hsjdbcn.org.
authors.forename: Jordi
authors.initials: J
authors.lastname: Anton
authors.affiliation: Paediatric Rheumatology Unit, Hospital Universitario y Politecnico La Fe, Valencia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Calvo
authors.affiliation: Department of Internal Medicine, Hospital Meixoeiro, Vigo, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Fernández-Martin
authors.affiliation: Department of Paediatric Rheumatology, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Mari Luz
authors.initials: ML
authors.lastname: Gamir
authors.affiliation: Department of Paediatric Rheumatology. Hospital La Paz, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Merino
authors.affiliation: Department of Paediatrics, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Jimenez-Treviño
authors.affiliation: Department of Paediatrics, Hospital Universitario San Cecilio, Granada, Spain.
authors.forename: Belen
authors.initials: B
authors.lastname: Sevilla
authors.affiliation: Department of Internal Medicine, Hospital de Vinaros, Vinaros, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Cabades
authors.affiliation: Paediatric Rheumatology Unit, Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues, and Department of Paediatrics, Corporacio Sanitaria Parc Taulí, Sabadell, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Bou
authors.affiliation: Department of Immunology-CDB, Hospital Clínic-IDIBAPS, Barcelona, Spain.
authors.forename: Juan I
authors.initials: JI
authors.lastname: Arostegui
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D054796:Drug Dosage Calculations; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000276:immunology; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010641:Phenotype; D012074:Remission Induction; D012307:Risk Factors; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002352:Carrier Proteins; C508585:IL1B protein, human; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C541220:canakinumab