title: Safety and efficacy of canakinumab in Japanese patients with phenotypes of cryopyrin-associated periodic syndrome as established in the first open-label, phase-3 pivotal study (24-week results).
abstract: OBJECTIVE
  Cryopyrin-associated periodic syndrome (CAPS), a rare hereditary auto-inflammatory disease, is associated with mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1 β) release. CAPS generally occurs in early childhood with most patients presenting with periodic fever, skin rash, osteoarthropathy, aseptic meningitis, sensorineural hearing loss and optic neuritis. Canakinumab, a fully human anti-IL-1β monoclonal antibody which binds selectively to IL-1β, has demonstrated good efficacy with CAPS. This is the first study to evaluate the safety and efficacy of canakinumab in Japanese patients with CAPS.
  
  
  METHODS
  In this open-label study, 19 Japanese CAPS patients aged ≥2 years received canakinumab either 150 mg s.c. or 2 mg/kg for patients with a body weight ≤ 40 kg every 8 weeks for 24 weeks. The primary objective was to assess the proportion of patients who were free of relapse at week 24.
  
  
  RESULTS
  A complete response was achieved in 18 (94.7%) patients with some requiring a dose and/or a frequency adjustment to attain full clinical response. The majority of patients (14/18; 77.8%) were in remission, i.e. free of relapse at week 24. Auto-inflammatory disease activity as assessed by physician's global assessment declined from baseline to end of the study (score of absent in 10.5% at baseline versus 31.6% at end of the study). Two patients had serious adverse events (SAEs), which resolved with standard treatment. One patient reported a mild injection-site reaction. No malignancies or deaths were reported during the study.
  
  
  CONCLUSIONS
  Canakinumab 150 mg s.c. every 8 weeks was well-tolerated, highly efficacious and offered a convenient dosing regimen for treating Japanese patients with CAPS.
authors: Department of Paediatrics, Yokohama City University, Yokohama, Japan. timagawa@gmail.com
authors: Tomoyuki
authors: T
authors: Imagawa
authors: Ryuta
authors: R
authors: Nishikomori
authors: Hidetoshi
authors: H
authors: Takada
authors: Saoko
authors: S
authors: Takeshita
authors: Neha
authors: N
authors: Patel
authors: Dennis
authors: D
authors: Kim
authors: Karine
authors: K
authors: Lheritier
authors: Toshio
authors: T
authors: Heike
authors: Toshiro
authors: T
authors: Hara
authors: Shumpei
authors: S
authors: Yokota
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D007279:Injections, Subcutaneous; D007564:Japan; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; C541220:canakinumab