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

Kuemmerle-Deschner JB, Tyrrell PN, Koetter I, Wittowski H, Bialkowski A, Tzaribachev N, Lohse P, Koitchev A, Deuter C, Foell D, Benseler SM

Zusammenfassung

BACKGROUND:: Muckle-Wells syndrome (MWS) is an inherited autoinflammatory disease caused by NLRP3 gene mutations which 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 report the short- and long-term efficacy and safety of anakinra therapy in children and adults with severe MWS. PATIENTS AND METHODS:: A single center observational study was performed. Standardized assessments included clinical features, the MWS disease activity score (MWS-DAS), classical and novel inflammatory markers, and patient-derived measures of health. Outcome: MWS-DAS <10 at 2 weeks and at last follow-up. Analysis: Measures of MWS disease activity were analyzed using descriptive statistics and paired comparative analysis. RESULTS:: A total of 12 patients with severe MWS (5 children, 7 adults) received anakinra for a median time of 11months (5-14). Disease activity was significantly lower in all patients at 2 weeks (p=0.0005). MWS organ manifestations improved, as did all patient-derived measures of health, inflammatory markers, and hearing loss in two patients. The novel neutrophil activation biomarker S100A12 followed clinical disease activity. Treatment was well tolerated, and no serious adverse events were observed. CONCLUSION:: Anakinra was a safe and effective treatment for severe MWS, leading to a significant improvement of disease activity at 2 weeks and long-term. Anakinra therapy therefore should be considered in children and adults with severe MWS disease requiring IL-1 blockade.