title: Treatment of Muckle-Wells syndrome: analysis of two IL-1-blocking regimens.
abstract: OBJECTIVE
  Muckle-Wells syndrome (MWS) is an autoinflammatory disease characterized by excessive interleukin-1 (IL-1) release, resulting in recurrent fevers, sensorineural hearing loss, and amyloidosis. IL-1 inhibition with anakinra, an IL-1 receptor antagonist, improves clinical symptoms and inflammatory markers. Subclinical disease activity is commonly observed. Canakinumab, a fully human IgG1 anti-IL-1β monoclonal antibody, can abolish excess IL-1β. The study aim was to analyze the efficacy and safety of these two anti-IL-1 therapies.
  
  
  METHODS
  Two cohorts of patients with severe MWS and confirmed NLRP3 mutation were treated with anakinra and/or canakinumab. Clinical and laboratory features including ESR, CRP, SAA, and the neutrophil marker S100A12 were determined serially. Disease activity was captured by MWS disease activity scores (MWS-DAS). Remission was defined as MWS-DAS ≤5 plus normal CRP and SAA. Treatment efficacy and safety were analyzed.
  
  
  RESULTS
  The study included 12 anakinra- and 14 canakinumab-treated patients; the median age was 33.5 years (3.0 years to 72.0 years); 57% were female patients. Both treatment regimens led to a significant reduction of clinical disease activity and inflammatory markers. At last follow-up, 75% of anakinra-treated and 93% of canakinumab-treated patients achieved remission. During follow-up, S100A12 levels mirrored recurrence of disease activity. Both treatment regimens had favorable safety profiles.
  
  
  CONCLUSIONS
  IL-1 blockade is an effective and safe treatment in MWS patients. MWS-DAS in combination with MWS inflammatory markers provides an excellent monitoring tool set. Canakinumab led to a sustained control of disease activity even after secondary failure of anakinra therapy. S100A12 may be a sensitive marker to detect subclinical disease activity.
authors.forename: Jasmin B
authors.initials: JB
authors.lastname: Kuemmerle-Deschner
authors.forename: Helmut
authors.initials: H
authors.lastname: Wittkowski
authors.forename: Pascal N
authors.initials: PN
authors.lastname: Tyrrell
authors.forename: Ina
authors.initials: I
authors.lastname: Koetter
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Katharina
authors.initials: K
authors.lastname: Ummenhofer
authors.forename: Fabian
authors.initials: F
authors.lastname: Reess
authors.forename: Sandra
authors.initials: S
authors.lastname: Hansmann
authors.forename: Assen
authors.initials: A
authors.lastname: Koitschev
authors.forename: Christoph
authors.initials: C
authors.lastname: Deuter
authors.forename: Anja
authors.initials: A
authors.lastname: Bialkowski
authors.forename: Dirk
authors.initials: D
authors.lastname: Foell
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Benseler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy*; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; C541220:canakinumab