title: Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study.
abstract: BACKGROUND
  To assess the effect of canakinumab, a fully human anti-interleukin-1β antibody, on symptoms and health-related quality of life (HRQoL) in patients with cryopyrin-associated periodic syndrome (CAPS).
  
  
  METHODS
  In this 48-week, phase 3 study, patients with CAPS received canakinumab 150 mg subcutaneously at 8-week intervals. All patients (n = 35) received canakinumab during weeks 1 through 8; weeks 9 through 24 constituted a double-blind placebo-controlled withdrawal phase, and weeks 24 through 48 constituted an open-label phase in which all patients received canakinumab. Patient and physician assessments of symptoms, levels of inflammatory markers, and HRQoL were performed.
  
  
  RESULTS
  Rapid symptom remission was achieved, with 89% of patients having no or minimal disease activity on day 8. Responses were sustained in patients receiving 8-weekly canakinumab. Responses were lost during the placebo-controlled phase in the placebo group and were regained on resuming canakinumab therapy in the open-label phase. Clinical responses were accompanied by decreases in serum levels of C-reactive protein, serum amyloid A protein, and interleukin-6. HRQoL scores at baseline were considerably below those of the general population. Improvements in all 36-item Short-Form Health Survey (SF-36) domain scores were evident by day 8. Scores approached or exceeded those of the general U.S. population by week 8 and remained stable during canakinumab therapy. Improvements in bodily pain and role-physical were particularly marked, increasing by more than 25 points from baseline to week 8. Therapy was generally well tolerated.
  
  
  CONCLUSIONS
  Canakinumab, 150 mg, 8-weekly, induced rapid and sustained remission of symptoms in patients with CAPS, accompanied by substantial improvements in HRQoL.
  
  
  BACKGROUND
  Clintrials.gov NCT00465985.
authors.affiliation: Centre de Référence des Maladies Autoinflammatoires, Hôpital Kremlin Bicetre, Paris University of Medicine, Le Kremlin Bicetre, Paris, France. isabelle.kone-paut@bct.aphp.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Koné-Paut
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Lachmann
authors.forename: Jasmin B
authors.initials: JB
authors.lastname: Kuemmerle-Deschner
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.forename: Kieron S
authors.initials: KS
authors.lastname: Leslie
authors.forename: Richard
authors.initials: R
authors.lastname: Mouy
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferreira
authors.forename: Karine
authors.initials: K
authors.lastname: Lheritier
authors.forename: Neha
authors.initials: N
authors.lastname: Patel
authors.forename: Ralph
authors.initials: R
authors.lastname: Preiss
authors.forename: Philip N
authors.initials: PN
authors.lastname: Hawkins
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006304:Health Status; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012074:Remission Induction; D000685:Serum Amyloid A Protein / Q000378:metabolism; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053583:Interleukin-1beta; D015850:Interleukin-6; D000685:Serum Amyloid A Protein; C541220:canakinumab; D002097:C-Reactive Protein