title: Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes.
abstract: OBJECTIVE
  Longer-term effects of prolonged selective interleukin-1β blockade with canakinumab were evaluated in the largest cohort of cryopyrin-associated periodic syndrome (CAPS) patients studied to date.
  
  
  METHODS
  Adult and paediatric CAPS patients (n=166, including canakinumab-naive and pretreated patients from previous studies) received canakinumab subcutaneously 150 mg or 2 mg/kg (≤40 kg) every 8 weeks for up to 2 years. Response and relapse was assessed using scores for disease activity, skin rash and C-reactive protein (CRP) and/or serum amyloid A (SAA) levels.
  
  
  RESULTS
  Complete response was achieved in 85 of 109 canakinumab-naive patients (78%; 79/85 patients within 8 days, and five patients between days 10 and 21). Of 141 patients with an available relapse assessment, 90% did not relapse, their CRP/SAA levels normalised (<10 mg/l) by day 8, and remained in the normal range thereafter. Median treatment duration was 414 days (29-687 days). Upward adjustments of dose or frequency were needed in 24.1% patients; mostly children and those with severe CAPS. Predominant adverse events (AE) were infections (65.7%) of mostly mild-to-moderate severity. Serious AE reported in 18 patients (10.8%) were mainly infections and were responsive to standard treatment. The majority of patients (92%) reported having no injection-site reactions and only 8% patients reported mild-to-moderate reactions. Patients receiving vaccination (15%) showed normal immune response.
  
  
  CONCLUSIONS
  Subcutaneous canakinumab 150 mg every 8 weeks was well tolerated and provided substantial disease control in children and adults across all CAPS phenotypes. Higher canakinumab doses in younger patients and more severe CAPS disease were efficacious in achieving complete responses without evidence of increased AE.
  
  
  BACKGROUND
  NCT00685373 (clinicaltrials.gov).
authors.affiliation: Division of Pediatric Rheumatology, Department of Pediatrics, University Hospital Tübingen, Germany. kuemmerle.deschner@uni-tuebingen.de
authors.forename: Jasmin B
authors.initials: JB
authors.lastname: Kuemmerle-Deschner
authors.forename: E
authors.initials: E
authors.lastname: Hachulla
authors.forename: R
authors.initials: R
authors.lastname: Cartwright
authors.forename: P N
authors.initials: PN
authors.lastname: Hawkins
authors.forename: T A
authors.initials: TA
authors.lastname: Tran
authors.forename: B
authors.initials: B
authors.lastname: Bader-Meunier
authors.forename: J
authors.initials: J
authors.lastname: Hoyer
authors.forename: M
authors.initials: M
authors.lastname: Gattorno
authors.forename: A
authors.initials: A
authors.lastname: Gul
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: K S
authors.initials: KS
authors.lastname: Leslie
authors.forename: S
authors.initials: S
authors.lastname: Jiménez
authors.forename: S
authors.initials: S
authors.lastname: Morell-Dubois
authors.forename: N
authors.initials: N
authors.lastname: Davis
authors.forename: N
authors.initials: N
authors.lastname: Patel
authors.forename: A
authors.initials: A
authors.lastname: Widmer
authors.forename: R
authors.initials: R
authors.lastname: Preiss
authors.forename: H J
authors.initials: HJ
authors.lastname: Lachmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001835:Body Weight; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007279:Injections, Subcutaneous; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D010641:Phenotype; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053583:Interleukin-1beta; C541220:canakinumab; D002097:C-Reactive Protein