title: A survey of resistance to colchicine treatment for French patients with familial Mediterranean fever.
abstract: Colchicine is the standard treatment for familial Mediterranean fever (FMF), preventing attacks and inflammatory complications. True resistance is rare and yet not clearly defined. We evaluated physicians' definition of colchicine resistance and report how they manage it.
  
  
  
  We recruited patients with a clinical diagnosis of FMF, one exon-10 Mediterranean fever (MEFV) gene mutation and considered resistant to colchicine, via networks of expert physicians. Clinical, biological characteristics and information about colchicine treatment (dose adjustment, compliance) were collected. The severity of FMF was assessed by the Tel Hashomer criteria.
  
  
  
  We included 51 patients, most females (55%), mean age 34 ± 23.1 years years (range 4.7-86.3). Overall, 58% (27/47) patients had homozygous M694 MEFV gene mutations. Seventeen of 42 patients (40%) declared full adherence to colchicine treatment, greater for children (48%) than adults (22%). Physicians considered colchicine resistance with > 6 attacks/year (n = 21/51, 42%), > 4 attacks in the last 6 months (n = 13/51, 26%), persistent inflammation (n = 23/51, 45%), renal amyloidosis in (n = 6/28, 22%) of adult patients and intolerance to an increase in colchicine dose (n = 10/51, 19%), and other reasons (n = 13/51, 23%), including chronic arthralgia (n = 6/51, 12%). Interleukin 1-targeting drugs represented the only alternative treatments in addition to daily colchicine.
  
  
  
  Resistance to colchicine is rare (<10% of patients) and mostly observed in severe MEFV genotypes. The main reasons for physicians assessing resistance were severe clinical symptoms, persistent subclinical inflammation, and secondary amyloidosis. Low adherence to colchicine treatment is a key component of resistance.
authors.affiliation: Department of Paediatrics Rheumatology, CEREMAI, Bicêtre Hospital, AP-HP, University of Paris SUD, Le Kremlin-Bicêtre, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Corsia
authors.affiliation: Internal medicine, CERAIF, Tenon hospital, AP-HP, University of Paris EsT, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Georgin-Lavialle
authors.affiliation: Paediatrics, CEREMAI, Mignot Hospital, Versailles-Le Chainay, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Hentgen
authors.affiliation: Internal medicine, Huriez hospital, University of Lille, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.affiliation: Internal medicine, CERAIF, Tenon hospital, AP-HP, University of Paris EsT, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Grateau
authors.affiliation: General Paediatrics, Robert Debré Hospital, AP-HP, University of Paris, Paris, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Faye
authors.affiliation: Paediatric rheumatology and immunology, CERHUMIP, Necker Hospital, University of Paris, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Quartier
authors.affiliation: Department of Paediatrics Rheumatology, CEREMAI, Bicêtre Hospital, AP-HP, University of Paris SUD, Le Kremlin-Bicêtre, France.
authors.forename: Linda
authors.initials: L
authors.lastname: Rossi-Semerano
authors.affiliation: Department of Paediatrics Rheumatology, CEREMAI, Bicêtre Hospital, AP-HP, University of Paris SUD, Le Kremlin-Bicêtre, France. Isabelle.kone-paut@aphp.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Koné-Paut
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003078:Colchicine / Q000627:therapeutic use*; D010505:Familial Mediterranean Fever / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005602:France; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D055815:Young Adult
chemical_list: D007375:Interleukin-1; D003078:Colchicine
keywords: Anti interleukin 1; Colchicine; Compliance; Familial Mediterranean fever; Resistance to treatment