[Familial mediterranean fever]. / Fièvre méditerranéenne familiale.

FAMILIAL MEDITERRANEAN FEVER. Familial mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease worldwide. The recurrence of stereotyped febrile attacks lasting less than 3 days, associated with acute abdominal pain and a biological inflammatory syndrome in a child from the Mediterranean area, should raise its diagnosis. The detection of mutations in MEVF gene (exon 10 mainly) confirms the diagnosis. Long-term treatment with colchicine prevents the occurrence of attacks, and the development of secondary amyloidosis in adulthood, the most severe complication. The pathophysiology is increasingly well understood, with a key role for interleukin 1 (IL1), allowing the emergence of specific targeting therapies. Thus, IL1-blocking agents are second-line treatments, restricted for the very limited cases of patients, with colchicine resistance or intolerance.

FIÈVRE MÉDITERRANÉENNE FAMILIALE. La fièvre méditerranéenne familiale (FMF) est la maladie auto-inflammatoire monogénique la plus fréquente dans le monde. La récurrence d'accès fébriles stéréotypés durant moins de trois jours associés à des douleurs abdominales intenses et un syndrome inflammatoire biologique chez un enfant originaire du bassin méditerranéen doit faire évoquer son diagnostic. Celui-ci est confirmé par la recherche de mutations dans l'exon 10 du gène MEVF. Le traitement par colchicine au long cours prévient la survenue des accès et l'apparition secondaire d'amylose inflammatoire à l'âge adulte, complication la plus grave. La physiopathologie est de mieux en mieux comprise, avec un rôle central de l'interleukine 1, permettant le développement de biothérapies ciblant spécifiquement cette cytokine. Ces traitements de seconde ligne sont réservés aux très rares cas de patients réfractaires ou intolérants à la colchicine.

Real-Life Indications of Interleukin-1 Blocking Agents in Hereditary Recurrent Fevers: Data From the JIRcohort and a Literature Review.

Background: Interleukin (IL)-1 inhibitors represent the main treatment in patients with colchicine-resistant/intolerant familial Mediterranean fever (crFMF), mevalonate kinase deficiency (MKD), and tumor necrosis factor receptor-associated periodic syndrome (TRAPS). However, the reasons for the use of IL-1 inhibitors in these diseases are still not completely clarified. Objective: Identify real-life situations that led to initiating anakinra or canakinumab treatment in hereditary recurrent fevers (HRFs), combining data from an international registry and an up-to-date literature review. Patients and Methods: Data were extracted from the JIRcohort, in which clinical information (demographic data, treatment, disease activity, and quality of life) on patients with FMF, MKD, and TRAPS was retrospectively collected. A literature search was conducted using Medline, EMBASE, and Cochrane databases. Results: Complete data of 93 patients with HRF (53.8% FMF, 31.2% MKD, and 15.1% TRAPS) were analyzed. Data from both the registry and the literature review confirmed that the main reasons for use of IL-1 blockers were the following: failure of previous treatment (n = 57, 61.3% and n = 964, 75.3%, respectively), persistence of disease activity with frequent attacks (n = 44, 47.3% and n = 1,023, 79.9%) and/or uncontrolled inflammatory syndrome (n = 46, 49.5% and n = 398, 31.1%), severe disease complication or associated comorbidities (n = 38, 40.9% and n = 390, 30.4%), and worsening of patients' quality of life (n = 36, 38.7% and n = 100, 7,8%). No reasons were specified for 12 (16.4%) JIRcohort patients and 154 (12%) patients in the literature. Conclusion: In the absence of standardized indications for IL-1 inhibitors in crFMF, MKD, and TRAPS, these results could serve as a basis for developing a treat-to-target strategy that would help clinicians codify the therapeutic escalation with IL-1 inhibitors.

The Use of Interleukine-1 Inhibitors in Familial Mediterranean Fever Patients: A Narrative Review.

Purpose: Familial Mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease characterized by recurrent attacks of fever and serositis. It is associated with mutation in pyrin inflammasome leading to interleukin-1 (IL-1) over secretion. Although colchicine is the first line treatment in FMF, 5-10% of patients are reported in literature as non-responders. Colchicine is not always well-tolerated due either to its direct toxicity or to co-morbidities that preclude the administration of its proper dosage. For these patients an alternative or additional treatment to colchicine is necessary. This literature review reports the published data regarding the use of IL-1 inhibitors in Familial Mediterranean Fever. Results: There is no uniform definition of colchicine resistance, but the different studies of treatment with IL-1 inhibitors provide evidence of IL-1 pathogenic role in colchicine-resistant FMF. IL-1 inhibition is an efficacious option for controlling and preventing flares -at least at the short term- in FMF patients who are insufficiently controlled with colchicine alone. Although canakinumab is the only approved drug in Europe for colchicine resistant FMF treatment, experience with anakinra is also substantial. In the absence of comparative studies both treatments seem to be an equal option for the management of these patients. Overall the safety profile of IL-1 inhibitors seems not different in FMF patients than in the other diseases and can be considered as globally safe. The main side effects are local injection site reactions and infections. Conclusion: IL-1 inhibitors have the potential to improve patient outcome even in FMF patients with co-morbidities or severe complications in whom inflammation control is difficult to achieve with colchicine alone. Nevertheless, current data are limited and further evaluation of long-term efficacy and safety of IL-1 inhibitors are necessary, in order to provide robust evidence in this domain.