Dr. Koetter has received consulting fees, speaking fees, and/or honoraria from Abbott, Roche, Chugai, Wyeth, Essex, UCB, Bristol-Myers Squibb, and Pfizer (less than $10,000 each).
Efficacy and safety of anakinra therapy in pediatric and adult patients with the autoinflammatory Muckle-Wells syndrome
Article first published online: 25 FEB 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 3, pages 840–849, March 2011
How to Cite
Kuemmerle-Deschner, J. B., Tyrrell, P. N., Koetter, I., Wittkowski, H., Bialkowski, A., Tzaribachev, N., Lohse, P., Koitchev, A., Deuter, C., Foell, D. and Benseler, S. M. (2011), Efficacy and safety of anakinra therapy in pediatric and adult patients with the autoinflammatory Muckle-Wells syndrome. Arthritis & Rheumatism, 63: 840–849. doi: 10.1002/art.30149
- Issue published online: 3 FEB 2011
- Article first published online: 25 FEB 2011
- Accepted manuscript online: 15 NOV 2010 12:00PM EST
- Manuscript Accepted: 4 NOV 2010
- Manuscript Received: 19 FEB 2010
- IKZF at the University of Muenster. Grant Number: Project Foe 2/005/06
- DFG. Grant Number: Project FO 35412-2
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.
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.
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.
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.