title: IL-1β biological treatment of familial Mediterranean fever.
abstract: Familial Mediterranean fever (FMF) is a recessive, autosomal, auto-inflammatory disorder characterised by brief, recurring, self-limited episodes of fever and serositis resulting in abdominal, chest, joint and muscular pain; it is the most common of the periodic hereditary fevers and mostly affects Mediterranean populations. Daily administration of colchicine, a tricyclic alkaloid with anti-microtubule and anti-inflammatory properties, prevents the recurrence of FMF attacks and the development of secondary (AA) amyloidosis, the major long-tem complication of FMF. Colchicine is generally safe and well-tolerated; nevertheless, 5-10 % of FMF patients do not respond to conventional treatment, while another 2-5 % of patients are colchicine-intolerant because of toxicity issues, leading physicians to search for alternative therapeutic strategies. Recent new insights into the mechanisms of auto-inflammation add further proof to the efficacy of IL-1 targeting drugs in colchicine non-responder/intolerant FMF patients. A systematic study of relevant literature through PubMed/Medline was performed in order to identify publications reporting IL-1β biological treatment of FMF. Treatment methods, comorbidities, clinical response and side effects in literature case reports were analysed, as well as recent advances in the pathogenesis of auto-inflammation mechanisms in FMF and the causes of colchicine resistance or toxicity in common clinical practice. The paradigmatic experience of an FMF patient with severe FMF mutations (M694V/M694V) suffering from colchicine toxicity and successfully treated with anakinra is also reported. The present data show that anti-IL-1β biological treatment is actually a therapeutic option for FMF patients unresponsive or intolerant to colchicine or in FMF patients with concomitant vasculitis.
authors: Periodic Fever Research Centre-National Reference Centre for FMF, Catholic University of the Sacred Heart, Rome, Italy.
authors: Alessandra
authors: A
authors: Soriano
authors: Elena
authors: E
authors: Verecchia
authors: Antonella
authors: A
authors: Afeltra
authors: Raffaele
authors: R
authors: Landolfi
authors: Raffaele
authors: R
authors: Manna
mesh_terms: D000686:Amyloidosis / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D000818:Animals; D003078:Colchicine / Q000009:adverse effects* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D010505:Familial Mediterranean Fever / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000276:immunology / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D003078:Colchicine