title: Colchicine failure in familial Mediterranean fever and potential alternatives: embarking on the anakinra trial.
abstract: Familial Mediterranean fever (FMF) is a genetic auto-inflammatory disease characterized by spontaneous short attacks of fever, elevated acute-phase reactants, and serositis. Approximately 5%-10% of FMF patients do not respond to colchicine treatment and another 5% are intolerant to colchicine because of side effects. Recently, following the discovery of the inflammasome and recognition of the importance of interleukin-1beta (IL-1beta) as the major cytokine involved in the pathogenesis of FMF, IL-1beta blockade has been suggested and tried sporadically to treat FMF, with good results. To date, case reports and small case series involving colchicine-resistant FMF patients and showing high efficacy of IL-1beta blockade have been reported. At the Israel Center for FMF at the Sheba Medical Centerthe first double-blind randomized placebo-controlled trial of anakinra in FMF patients who are resistant or intolerant to colchicines is underway. In this report we discuss the mechanism of colchicine resistance in FMF patients, the data in the literature on IL1beta blockade in these patients, and the anakinra trial inclusion criteria and study protocol.
authors: Ilan
authors: I
authors: Ben-Zvi
authors: Avi
authors: A
authors: Livneh
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D002985:Clinical Protocols; D003078:Colchicine / Q000008:administration & dosage / Q000009:adverse effects; D003598:Cytoskeletal Proteins / Q000235:genetics; D004311:Double-Blind Method; D004351:Drug Resistance; D010505:Familial Mediterranean Fever / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006801:Humans; D058847:Inflammasomes; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000009:adverse effects; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D007557:Israel; D008297:Male; D008875:Middle Aged; D000071198:Pyrin; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; C000604192:MEFV protein, human; D000071198:Pyrin; D003078:Colchicine