title: Efficacy and safety of anakinra therapy in pediatric and adult patients with the autoinflammatory Muckle-Wells syndrome.
abstract: OBJECTIVE
  Muckle-Wells syndrome (MWS) is an inherited autoinflammatory disease caused by mutations in the NLRP3 gene that result in excessive interleukin-1 (IL-1) release. It is characterized by severe fevers, rashes, arthralgia, and conjunctivitis, leading to sensorineural deafness and amyloidosis. The recombinant IL-1 receptor antagonist anakinra blocks the biologic activity of IL-1. The aim of this study was to determine the short- and long-term efficacy and safety of anakinra therapy in children and adults with severe MWS.
  
  
  METHODS
  A single-center observational study was performed. Standardized assessments included clinical features, the Disease Activity Score (DAS) for MWS, classic and novel markers of inflammation, and patient-derived measures of health status. The primary outcome was a score of <10 on the DAS for MWS at 2 weeks and at the last followup visit. Measures of MWS disease activity were investigated using descriptive statistics and paired comparative analysis.
  
  
  RESULTS
  A total of 12 patients with severe MWS (5 children and 7 adults) received anakinra for a median of 11 months (range 5-14 months). The median followup was 11 months (range 5-14 months). Disease activity was significantly lower in all patients at 2 weeks (P = 0.0005). Organ manifestations of MWS improved, as did all patient-derived measures of health status, markers of inflammation, and hearing loss in 2 of the patients. Levels of the novel neutrophil activation biomarker S100A12 followed clinical disease activity. Treatment was well tolerated, and no serious adverse events were observed.
  
  
  CONCLUSIONS
  Anakinra was found to be a safe and effective treatment of severe MWS, leading to a significant improvement in disease activity at 2 weeks as well as long-term. Anakinra therapy should therefore be considered in children and adults with severe MWS disease requiring IL-1 blockade.
authors.affiliation: University Hospital Tübingen, Tübingen, Germany. kuemmerle.deschner@uni-tuebingen.de
authors.forename: Jasmin B
authors.initials: JB
authors.lastname: Kuemmerle-Deschner
authors.forename: Pascal N
authors.initials: PN
authors.lastname: Tyrrell
authors.forename: Ina
authors.initials: I
authors.lastname: Koetter
authors.forename: Helmut
authors.initials: H
authors.lastname: Wittkowski
authors.forename: Anja
authors.initials: A
authors.lastname: Bialkowski
authors.forename: Nicolai
authors.initials: N
authors.lastname: Tzaribachev
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Assen
authors.initials: A
authors.lastname: Koitchev
authors.forename: Christoph
authors.initials: C
authors.lastname: Deuter
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; D000367:Age Factors; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D002352:Carrier Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human