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

Abstract：

OBJECTIVES: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

journal_name

Arthritis Res Ther

journal_title

Arthritis research & therapy

authors

Kuemmerle-Deschner JB,Wittkowski H,Tyrrell PN,Koetter I,Lohse P,Ummenhofer K,Reess F,Hansmann S,Koitschev A,Deuter C,Bialkowski A,Foell D,Benseler SM

doi

10.1186/ar4237

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

R64

issue

3

eissn

1478-6354

issn

1478-6362

pii

ar4237

journal_volume

15

pub_type

杂志文章

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