Unresponsiveness to Colchicine Therapy in Patients with Familial Mediterranean Fever Homozygous for the M694V Mutation

Söylemezoğlu, Oğuz; Arga, Mustafa; Fidan, Kibriya; Gönen, Sevim; Emeksiz, Hamdi Cihan; Hasanoğlu, Enver; Buyan, Necla

doi:10.3899/jrheum.090273

Cited by 46 publications

(34 citation statements)

References 47 publications

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“…Only minimal genotype/phenotype correlations have emerged, and we tend not to draw much attention to them with our patients, as we feel that the exact MEFV mutation is not the sole determinant of clinical severity or colchicine response. 2 Homozygosity for the M694V mutation has been associated with relative resistance to colchicine, 10 and we have observed this occasionally as well. Similarly, certain mutations are said to be more associated with amyloidosis than others.…”

Section: Molecular Genetic Testingsupporting

confidence: 69%

Diagnosis and management of familial Mediterranean fever: Integrating medical genetics in a dedicated interdisciplinary clinic

Zadeh

Getzug²,

Grody

2011

Genetics in Medicine

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Familial Mediterranean fever is an autosomal recessive genetic disorder characterized by recurrent febrile polyserositis, especially prevalent in individuals of Mediterranean descent. Familial Mediterranean fever can have nonspecific manifestations that mimic many common acquired disorders such as infections, acute appendicitis, cholecystitis, and arthritis, which can delay diagnosis for many years and subject patients to extensive evaluations and even unnecessary surgery. Untreated familial Mediterranean fever can result in serious complications such as end-stage renal disease and malabsorption secondary to amyloid deposition in the kidneys and digestive tract, male and female infertility, and growth retardation in children. These significant sequelae, along with the episodic acute attacks, are readily preventable by treatment with oral colchicine and underscore the necessity of early detection and treatment from a medical, psychosocial, and economic standpoint. We describe our comprehensive approach to the accurate diagnosis and effective management of this disorder by means of a dedicated familial Mediterranean fever clinic that incorporates medical genetics on equal footing with general medicine. In addition to providing the clinician with the presenting features of familial Mediterranean fever, methods of diagnosis including molecular testing, and current management based on our extensive experience with hundreds of affected individuals, we also advance this approach as a model for the incorporation of medical genetics practice into the more traditional domains of general medicine. Genet Med 2011:13(3):263-269.

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Section: Molecular Genetic Testingsupporting

confidence: 69%

Diagnosis and management of familial Mediterranean fever: Integrating medical genetics in a dedicated interdisciplinary clinic

Zadeh

Getzug²,

Grody

2011

Genetics in Medicine

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“…Recently, Omenetti et al [17] have showed that IL1 secretion increased with both the number and penetrance of mutations, confirming the studies showing increased requirement of colchicine dosage and unresponsiveness in patients with homozygous M694V [18,19].…”

Section: Discussionmentioning

confidence: 77%

Treatment of colchicine-resistant Familial Mediterranean fever in children and adolescents

et al. 2015

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Familial Mediterranean fever (FMF) is the most common autoinflammatory disease worldwide. Approximately 5-10 % of patients are unresponsive to colchicine. Aim of this study was to determine the short- and long-term efficacy and safety of anti-interleukin 1 (anti-IL1) and anti-tumor necrosis factor agents in colchicine-resistant FMF cases in Turkish children and adolescents. This is a single-center retrospective case series of colchicine-resistant FMF patients. The included patients were treated with biologics for either colchicine resistance or because of one of the following: (1) amyloidosis, (2) recurrent prolonged febrile myalgia and frequent need of steroid and (3) persistent arthritis. Colchicine resistance was defined as at least one attack per month for three consecutive months and elevated erythrocyte sedimentation rate or C-reactive protein or serum amyloid A in-between attacks despite taking adequate dose of colchicine. Response to biologicals was evaluated by the Autoinflammatory Diseases Activity Index (AIDAI) score sheet, patients/parents'/physicians' global assessment of disease severity and laboratory parameters every 3-6 months. Fourteen patients were included in the study. Three patients were treated with etanercept for median 7 months (range 3-11 months), and all patients had to be switched to anti-IL1 treatment because of adverse effects and/or partial response. Eleven patients were treated with anakinra with a median duration of 8 months (4-60 months). Nine patients responded to treatment at the third month, but four of them switched to canakinumab because of noncompliance, local side effects and active arthritis. Nine patients were treated with canakinumab, all responded. At follow-up, in two patients the dose had to be increased, and on the other hand, in three patients the interval was increased to every 12-16 weeks. In three patients, anti-IL1 treatment could be stopped and they are fine with colchicine. This case series describes the largest cohort of colchicine-resistant FMF patients in childhood and adolescence. Anti-IL1 treatment is a safe and effective therapy to control inflammation. The treatment should be modified and decided for each patient on an individual basis.

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“…AAA patogenezinde TNF-α'nın rolünün aydınlatılması ile birlikte kolşisine yanıtsız hastalarda TNF-α blokerleri denenebilir. 8 Oral kolşi-sine yanıt vermeyen hastalarda anti TNF-α ajanların kullanımı konusunda sınırlı sayıda vaka bildirilmiştir.…”

Section: Discussionunclassified

Etanercept Treatment in Familial Mediterranean Fever Accompanied By Ankylosing Spondylitis: Case Report

Sanmak¹,

Mesci²,

Külcü³

2016

Turkiye Klinikleri J Case Rep

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Unresponsiveness to Colchicine Therapy in Patients with Familial Mediterranean Fever Homozygous for the M694V Mutation

Abstract: Our results indicate that the M694V/M694V mutation is associated with lower response to colchicine treatment. Therefore, patients homozygous for M694V/M694V may be carrying an increased risk for development of amyloidosis.

Cited by 46 publications

References 47 publications

Diagnosis and management of familial Mediterranean fever: Integrating medical genetics in a dedicated interdisciplinary clinic

Diagnosis and management of familial Mediterranean fever: Integrating medical genetics in a dedicated interdisciplinary clinic

Treatment of colchicine-resistant Familial Mediterranean fever in children and adolescents

Etanercept Treatment in Familial Mediterranean Fever Accompanied By Ankylosing Spondylitis: Case Report

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