title: Canakinumab (ACZ885, a fully human IgG1 anti-IL-1β mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS).
abstract: BACKGROUND
  Cryopyrin-associated periodic syndrome (CAPS) represents a spectrum of three auto-inflammatory syndromes, familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome (NOMID/CINCA) with etiology linked to mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1β) release. CAPS is a rare hereditary auto-inflammatory disease, which may start early in childhood and requires a life-long treatment. Canakinumab, a fully human anti-IL-1β antibody, produces sustained selective inhibition of IL-1β. This study was conducted to assess the efficacy, safety, and pharmacokinetics of canakinumab in the treatment of pediatric CAPS patients.
  
  
  METHODS
  Seven pediatric patients (five children and two adolescents) with CAPS were enrolled in a phase II, open-label study of canakinumab in patients with CAPS. Canakinumab was administered at a dose of 2 mg/kg subcutaneously (s.c.) (for patients with body weight ≤ 40 kg) or 150 mg s.c. (for patients with body weight > 40 kg) with re-dosing upon each relapse. The primary efficacy variable was time to relapse following achievement of a complete response (defined as a global assessment of no or minimal disease activity and no or minimal rash and values for serum C-reactive protein (CRP) and/or serum amyloid A (SAA) within the normal range, < 10 mg/L).
  
  
  RESULTS
  All patients achieved a complete response within seven days after the first dose of canakinumab and responses were reinduced on retreatment following relapse. Improvements in symptoms were evident within 24 hours after the first dose, according to physician assessments. The estimated median time to relapse was 49 days (95% CI 29 to 68) in children who received a dose of 2 mg/kg. Canakinumab was well tolerated. One serious adverse event, vertigo, was reported, but resolved during treatment.
  
  
  CONCLUSIONS
  Canakinumab, 2 mg/kg or 150 mg s.c., induced rapid and sustained clinical and biochemical responses in pediatric patients with CAPS.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00487708.
authors.affiliation: Division of Pediatric Rheumatology, Department of Pediatrics, University Children's Hospital Tuebingen, Hoppe-Seyler-Strasse 1, 72076 Tübingen, Tuebingen, Germany. kuemmerle.deschner@uni-tuebingen.de
authors.forename: Jasmin B
authors.initials: JB
authors.lastname: Kuemmerle-Deschner
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ramos
authors.forename: Norbert
authors.initials: N
authors.lastname: Blank
authors.forename: Joachim
authors.initials: J
authors.lastname: Roesler
authors.forename: Sandra D
authors.initials: SD
authors.lastname: Felix
authors.forename: Thomas
authors.initials: T
authors.lastname: Jung
authors.forename: Kirstin
authors.initials: K
authors.lastname: Stricker
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Stacey
authors.initials: S
authors.lastname: Tannenbaum
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Wright
authors.forename: Christiane
authors.initials: C
authors.lastname: Rordorf
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D053583:Interleukin-1beta; C541220:canakinumab