title: Efficacy and safety of canakinumab therapy in paediatric patients with cryopyrin-associated periodic syndrome: a single-centre, real-world experience.
abstract: OBJECTIVE
  The aim of this study was to determine the short- and long-term efficacy and safety of 8-weekly canakinumab therapy in children with cryopyrin-associated periodic syndromes (CAPS) in routine clinical practice.
  
  
  METHODS
  A single-centre observational study was performed. Patients were assessed every 8 weeks at a dedicated clinic. Standardized assessments were the 10-domains DAS for CAPS, acute phase reactants (APRs), physician's global assessment of disease activity, Child Health Assessment Questionnaire (CHAQ) and Child Health Questionnaire Parent Form 28 (CHQPF-28). The primary endpoint was clinical improvement, defined as a reduction of DAS score 8 weeks after commencing therapy. Secondary endpoints included sustained clinical improvement in APRs, relapses, CHAQ score and CHQPF-28 score.
  
  
  RESULTS
  Ten children with CAPS [eight Muckle-Wells syndrome (MWS), two chronic infantile cutaneous neurological articular (CINCA); median age 6.3 years] received 8-weekly canakinumab treatments at 2-8.7 mg/kg for a median of 21 months (range 12-31 months). Nine of 10 patients improved after the first dose: baseline median DAS of 7.5/20 decreased to 3.5/20 at 8 weeks (P = 0.04). This clinical improvement was sustained at a median follow-up of 21 months (range 12-31 months). Children with CINCA required higher doses of canakinumab than those with MWS. CHAQ and CHQ scores indicated improvement in functioning and health-related quality of life (HRQoL). Treatment was well tolerated, with no injection site reactions and no serious infections.
  
  
  CONCLUSIONS
  Canakinumab, although costly, is a safe and effective treatment for CAPS in children, leading to sustained improvement in disease activity, serological markers, functional ability and HRQoL.
authors.affiliation: Department of Rheumatology, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK. p.brogan@ucl.ac.uk.
authors.forename: Ricardo A G
authors.initials: RA
authors.lastname: Russo
authors.forename: Sonia
authors.initials: S
authors.lastname: Melo-Gomes
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Lachmann
authors.forename: Karen
authors.initials: K
authors.lastname: Wynne
authors.forename: Kaukab
authors.initials: K
authors.lastname: Rajput
authors.forename: Despina
authors.initials: D
authors.lastname: Eleftheriou
authors.forename: Clive
authors.initials: C
authors.lastname: Edelsten
authors.forename: Philip N
authors.initials: PN
authors.lastname: Hawkins
authors.forename: Paul A
authors.initials: PA
authors.lastname: Brogan
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006454:Hemoglobins / Q000276:immunology; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D008297:Male; D000685:Serum Amyloid A Protein / Q000276:immunology; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006454:Hemoglobins; D053583:Interleukin-1beta; D000685:Serum Amyloid A Protein; C541220:canakinumab; D002097:C-Reactive Protein
keywords: CAPS; CINCA/NOMID; Muckle-Wells; autoinflammatory; canakinumab