title: Efficacy and safety of canakinumab in Schnitzler syndrome: A multicenter randomized placebo-controlled study.
abstract: BACKGROUND
  Schnitzler syndrome is an adult-onset autoinflammatory disease characterized by urticarial exanthema and monoclonal gammopathy accompanied by systemic symptoms such as fever, bone, and muscle pain. Up to now, approved treatment options are not available.
  
  
  OBJECTIVE
  We assessed effects of the anti-IL-1β mAb canakinumab on the clinical signs and symptoms of Schnitzler syndrome.
  
  
  METHODS
  In this phase II, randomized placebo-controlled multicenter study, 20 patients with active disease enrolled in 4 German study centers. Patients were randomly assigned to receive single subcutaneous canakinumab 150 mg or placebo injections for 7 days, followed by a 16-week open-label phase with canakinumab injections on confirmed relapse of symptoms. The primary end point was the proportion of patients with complete clinical response evaluated by physician global assessment at day 7. Key secondary end points included changes in patient-reported disease activity (Schnitzler activity score), inflammation markers (C-reactive protein and serum amyloid A), and quality-of-life assessments (Dermatology Life Quality Index and 36-item short form health survey).
  
  
  RESULTS
  The proportion of patients with complete clinical response at day 7 was significantly higher (P = .001) in the canakinumab-treated group (n = 5 of 7) than in the placebo group (n = 0 of 13). Levels of inflammation markers C-reactive protein and serum amyloid A and quality-of-life scores were significantly reduced in canakinumab-treated but not in placebo-treated individuals. Positive effects continued up to 16 weeks. Adverse events were manageable and included respiratory tract infections, gastrointestinal symptoms, and hypertension.
  
  
  CONCLUSIONS
  In this first placebo-controlled study, canakinumab was effective in patients with Schnitzler syndrome, and thus canakinumab may be further evaluated as a therapeutic option for this rare disease.
authors.affiliation: Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany; Autoinflammation Reference Center Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany. Electronic address: karoline.krause@charite.de.
authors.forename: Karoline
authors.initials: K
authors.lastname: Krause
authors.affiliation: Department of Dermatology, Universitätsklinikum Münster, Münster, Germany.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Tsianakas
authors.affiliation: Department of Dermatology, Klinikum Darmstadt, Darmstadt, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Wagner
authors.affiliation: Department of Dermatology and Allergy, Universitätsklinik Tübingen, Tübingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Fischer
authors.affiliation: Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Weller
authors.affiliation: Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Metz
authors.affiliation: Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Church
authors.affiliation: Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany; Autoinflammation Reference Center Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002097:C-Reactive Protein / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D019873:Schnitzler Syndrome / Q000188:drug therapy*; D000685:Serum Amyloid A Protein / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000685:Serum Amyloid A Protein; C541220:canakinumab; D002097:C-Reactive Protein
keywords: Autoinflammatory; IL-1; Schnitzler syndrome; canakinumab; urticaria