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Treatment of Muckle-Wells syndrome: analysis of two IL-1-blocking regimens

Jasmin B Kuemmerle-Deschner1*, Helmut Wittkowski2, Pascal N Tyrrell3, Ina Koetter4, Peter Lohse5, Katharina Ummenhofer1, Fabian Reess1, Sandra Hansmann1, Assen Koitschev6, Christoph Deuter7, Anja Bialkowski1, Dirk Foell8 and Susanne M Benseler3

Author Affiliations

1 Division of Pediatric Rheumatology, Department of Pediatrics, University Hospital Tuebingen, Germany

2 Department of General Pediatrics, University Children's Hospital Muenster, Germany

3 Division of Rheumatology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada

4 Division of Rheumatology, Department of Internal Medicine, University Hospital Tuebingen, Germany

5 Institut fuer Labormedizin, Prof. Blessing, Bereich Molekularmedizin-Singen, Germany

6 Pediatric Otorhinolaryngology, Klinikum Stuttgart-Olgahospital, Germany

7 Centre for Ophthalmology, University Hospital Tuebingen, Germany

8 Institute of Immunology, University of Muenster, Germany

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Arthritis Research & Therapy 2013, 15:R64  doi:10.1186/ar4237

Published: 29 May 2013



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.


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.


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.


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.

NLRP3; CIAS1; mutation; Muckle-Wells syndrome; autoinflammatory fever syndromes; interleukin-1 inhibition; anakinra; canakinumab; S100A12