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Arthritis Research and Therapy

, 15:R64

First Online: 29 May 2013Received: 19 September 2012Revised: 17 February 2013Accepted: 29 May 2013


ObjectivesMuckle-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.

MethodsTwo 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.

ResultsThe 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.

ConclusionsIL-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.

KeywordsNLRP3 CIAS1 mutation Muckle-Wells syndrome autoinflammatory fever syndromes interleukin-1 inhibition anakinra canakinumab S100A12 AbbreviationsAnti-IL-1β blcanakinumab treatment at baseline

anti-IL-1β lfupcanakinumab treatment at last follow-up

CAPScryopyrin-associated periodic syndrome

CIAS1cold-induced autoinflammatory syndrome 1

CINCAchronic infantile neurologic cutaneous and articular syndrome

CRPc-reactive protein

ELISAenzyme-linked immunosorbent assay

ESRerythrocyte sedimentation rate

FCASfamilial cold autoinflammatory syndrome

FMFfamilial Mediterranean fever


IgG1immunoglobulin G1



IL-1RAIL-1-receptor antagonist

IL-1Ra blIL-1-receptor antagonist treatment at baseline

IL-1Ra lfupIL-1-receptor antagonist treatment at last follow-up

IL-1RIIL-1-receptor type 1

MWSMuckle-Wells syndrome

MWS-DASMuckle-Wells syndrome Disease Activity Score

NLRP3-NALP3NOD-like receptor family, pyrin domain containing 3

NOMIDneonatal onset, multisystem inflammatory disease

PLTplatelet count

S100A12also named EN-RAGE and calgranulin

SAAserum amyloid A

sJIAsystemic juvenile idiopathic arthritis.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4237 contains supplementary material, which is available to authorized users.

Jasmin B Kuemmerle-Deschner, Helmut Wittkowski, Dirk Foell and Susanne M Benseler contributed equally to this work.

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Autor: Jasmin B Kuemmerle-Deschner - Helmut Wittkowski - Pascal N Tyrrell - Ina Koetter - Peter Lohse - Katharina Ummenhofer - Fa


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