Biologic agents
Interleukin-1 Targeting Drugs in Familial Mediterranean Fever: A Case Series and a Review of the Literature

https://doi.org/10.1016/j.semarthrit.2010.11.003Get rights and content

Objectives

Familial Mediterranean fever (FMF) is an autosomal-recessive autoinflammatory disorder common in Mediterranean populations. FMF is associated with mutations of the MEFV gene, which encodes pyrin. Functional studies suggest that pyrin is implicated in the maturation and secretion of IL-1. The IL-1 receptor antagonist or anti-IL1 monoclonal antibody may therefore represent a new approach to treat FMF. The aim of this report was to evaluate and discuss treatment of FMF with interleukin-1 targeting drugs.

Methods

Electronic mailing lists of French pediatric and adult rheumatologist associations were used to call for FMF patients treated with interleukin-1 antagonists. A search for published FMF patients treated with interleukin-1 targeting drugs was performed by screening PubMed.

Results

Here, we report 7 cases of FMF patients treated with anakinra and/or canakinumab and discuss the clinical situations that may indicate the use of IL-1 blocking agents in FMF. The use of interleukin-1 targeting drugs was beneficial to all patients. The reasons for using interleukin-1 targeting drugs in FMF patients were as follows: (1) incomplete control of disease activity despite colchicine treatment; (2) high serum amyloid A levels despite colchicine treatment; (3) impossibility to use colchicine treatment because of severe side effects; (4) FMF in association with vasculitis.

Conclusions

Interleukin-1 targeting drugs may be good candidates when looking for an alternative or supplementary treatment to colchicine. These observations highlight the need for controlled trials to further evaluate the safety and efficacy of interleukin-1 antagonists in FMF patients.

Section snippets

Methods

Electronic mailing lists of French pediatric and adult rheumatologists societies were used to call for the medical history of FMF patients (confirmed by carriage of 2 MEFV-mutations) who had been treated with interleukin-1 targeting drugs. Information about age, sex, disease course, treatment before anti-IL-1 targeting drugs, reasons for the use of anti-IL-1 targeting drugs, treatment modalities, clinical effect, side effects, and duration of follow-up were recorded. As the genetic analyses

Results

Seven patients (4 male, 3 female) from 5 different hospitals were identified. The patients' ages when starting IL-1 targeting drugs were 51, 45, 12, and 7 years (4 patients). Disease duration before the use of interleukin-1 targeting drugs was 3 to 6 years in children and approximately 20 years in adult patients. MEFV gene analyses showed homozygote M694V mutations in 6 patients and composite I692de/V726A, E149Q mutations in 1 patient (case 4). FMF manifested with fever and abdominal pain in

Discussion

Here, we report 7 FMF patients who were treated with interleukin-1 targeting drugs. Additionally, in the literature 8 single cases have been published (9, 10, 11, 12, 13, 14, 15, 16). Considering all published cases, the reasons for using interleukin-1 targeting drugs in FMF patients can be divided into the following categories: (1) incomplete control of FMF disease activity despite colchicine treatment; (2) high SAA levels and/or renal complications despite colchicine treatment; (3)

Conclusions

Colchicine treatment is safe and effective in the large majority of FMF patients. However, the published cases indicate that in some, rare patients the availability of an alternative treatment would be desirable. The data for the use of interleukin-1 targeting drugs in FMF patients are currently limited to uncontrolled off-label use. Altogether, the published cases indicate that interleukin-1 targeting drugs may be good candidates when looking for a treatment alternative to or supplementary to

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    IKP received research and consulting fees for lecturing (<10,000 Euros) from Novartis Pharma.

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