Efficacy and safety of anakinra therapy in pediatric and adult patients with the autoinflammatory Muckle-Wells syndrome

Arthritis Rheum. 2011 Mar;63(3):840-9. doi: 10.1002/art.30149.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / adverse effects*
  • Biomarkers / metabolism
  • Carrier Proteins / genetics
  • Child
  • Child, Preschool
  • Cryopyrin-Associated Periodic Syndromes / drug therapy*
  • Cryopyrin-Associated Periodic Syndromes / genetics
  • Cryopyrin-Associated Periodic Syndromes / immunology
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / administration & dosage*
  • Interleukin 1 Receptor Antagonist Protein / adverse effects*
  • Male
  • Middle Aged
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Treatment Outcome
  • Young Adult


  • Antirheumatic Agents
  • Biomarkers
  • Carrier Proteins
  • Interleukin 1 Receptor Antagonist Protein
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human