Longterm Beneficial Effect of Canakinumab in Colchicine-resistant Familial Mediterranean Fever

Laskari, Katerina; Boura, Panagiota; Dalekos, George Ν.; Garyfallos, Alexandros; Karokis, D; Pikazis, Dimitrios; Settas, Loukas; Skarantavos, G.; Tsitsami, Elena; Sfikakis, Petros P.

doi:10.3899/jrheum.160518

Cited by 47 publications

(25 citation statements)

References 25 publications

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“…All patients responded to the treatment but four relapsed during the follow-up. The shortening of Canakinumab administration intervals from 8/6 weeks to 4 weeks resulted in partial to full clinical remission (Laskari et al, 2017). …”

Section: Skin Diseases With Il-1 Involvementmentioning

confidence: 99%

Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases

2017

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In 2002, intracellular protein complexes known as the inflammasomes were discovered and were shown to have a crucial role in the sensing of intracellular pathogen- and danger-associated molecular patterns (PAMPs and DAMPs). Activation of the inflammasomes results in the processing and subsequent secretion of the pro-inflammatory cytokines IL-1β and IL-18. Several autoinflammatory disorders such as cryopyrin-associated periodic syndromes and Familial Mediterranean Fever have been associated with mutations of genes encoding inflammasome components. Moreover, the importance of IL-1 has been reported for an increasing number of autoinflammatory skin diseases including but not limited to deficiency of IL-1 receptor antagonist, mevalonate kinase deficiency and PAPA syndrome. Recent findings have revealed that excessive IL-1 release induced by harmful stimuli likely contributes to the pathogenesis of common dermatological diseases such as acne vulgaris or seborrheic dermatitis. A key pathogenic feature of these diseases is IL-1β-induced neutrophil recruitment to the skin. IL-1β blockade may therefore represent a promising therapeutic approach. Several case reports and clinical trials have demonstrated the efficacy of IL-1 inhibition in the treatment of these skin disorders. Next to the recombinant IL-1 receptor antagonist (IL-1Ra) Anakinra and the soluble decoy Rilonacept, the anti-IL-1α monoclonal antibody MABp1 and anti-IL-1β Canakinumab but also Gevokizumab, LY2189102 and P2D7KK, offer valid alternatives to target IL-1. Although less thoroughly investigated, an involvement of IL-18 in the development of cutaneous inflammatory disorders is also suspected. The present review describes the role of IL-1 in diseases with skin involvement and gives an overview of the relevant studies discussing the therapeutic potential of modulating the secretion and activity of IL-1 and IL-18 in such diseases.

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Section: Skin Diseases With Il-1 Involvementmentioning

confidence: 99%

Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases

2017

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“…Its effi cacy and safety were confi rmed by case reports, case report series or even doubleblind, randomized, placebo-controlled studies in both children and adults. Clinical response and full remission were observed in the majority of involved patients (11)(12)(13)(14)(15). Moreover, in certain cases, the drug administration interval was safely increased during the remission from 4 to 6-8 weeks (15).…”

Section: Discussionmentioning

confidence: 95%

Canakinumab as monotherapy for treatment of familial Mediterranean fever – first report in Central and Eastern Europe region

Jeseňák¹,

Hrubisková²,

Kapustova³

et al. 2018

BLL

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Autoinflammatory disorders (AID) are characterized by spontaneous attacks of acute inflammation with a broad spectrum of clinical symptoms. Ongoing inflammation and reoccurrence of acute flares can lead to the development of amyloidosis. One group of AID is represented by monogenic periodic fever syndromes while familial Mediterranean fever (FMF) is the most common form of AID from this group. Its prevalence in Central and Eastern Europe was reported to be very low. We report a case of FMF patient with a very severe clinical course of FMF and intolerance to colchicine, which is a gold standard for FMF treatment. The clinical effect of the application of anakinra was insufficient and accompanied with side effects and low tolerability. Switching to canakinumab (human monoclonal antibody against IL-1β) at dose of 150 mg every 4 weeks induced a rapid remission of the disease activity and inflammatory markers. However, due to relapse of acute flares after three weeks from application, the escalation of dose to 300 mg every 4 weeks induced a complete remission of symptoms and significantly improved the quality of life. This is the first report of successful canakinumab administration in FMF patient in Central and Eastern Europe, a region with very low incidence of FMF (Tab. 1, Ref. 16).

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“…11,12,22 Renal amyloidosis remains the leading cause of increased mortality in adults with FMF even after the introduction of routine colchicine therapy. 27 The recent randomised controlled CLUSTER trial strengthened this idea, with the demonstration of the effectiveness of canakinumab at controlling flares and disease control compared with standard of care in colchicine-resistant FMF. 25,26 The response of patients with colchicine-resistant FMF to the neutralising anti-IL-1β antibody canakinumab suggests that IL-1β is a key cytokine in this disorder.…”

Section: Periodic Fevermentioning

confidence: 99%

Monogenic autoinflammatory disorders: beyond the periodic fever

Moghaddas

2020

Internal Medicine Journal

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The past two decades have seen an exponential increase in the number of monogenic autoinflammatory disorders described, coinciding with improved genetic sequencing techniques. This group of disorders has evolved to be heterogeneous and certainly more complex than the original four ‘periodic fever syndromes’ caused by innate immune over‐activation. This review aims to provide an update on the classic periodic fever syndromes as well as introducing the broadening spectrum of clinical features seen in more recently described conditions.

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Longterm Beneficial Effect of Canakinumab in Colchicine-resistant Familial Mediterranean Fever

Abstract: Treatment with canakinumab in an individualized dosing scheme results in rapid and sustained remission in colchicine-resistant FMF.

Cited by 47 publications

References 25 publications

Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases

Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases

Canakinumab as monotherapy for treatment of familial Mediterranean fever – first report in Central and Eastern Europe region

Monogenic autoinflammatory disorders: beyond the periodic fever

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