title: Anakinra for Colchicine-Resistant Familial Mediterranean Fever: A Randomized, Double-Blind, Placebo-Controlled Trial.
abstract: Familial Mediterranean fever (FMF) is refractory to colchicine prophylaxis in 10-20% of patients. In a number of patient series, treatment with anakinra, an interleukin-1-blocking agent, prevented FMF attacks in those with colchicine-resistant FMF. This study was undertaken to evaluate the efficacy and safety of anakinra in the treatment of colchicine-resistant FMF, using a randomized controlled trial.
  
  
  
  Patients with colchicine-resistant FMF receiving colchicine (dosage ≥1.5 to ≤3 mg/day) were recruited and randomly assigned to receive anakinra or placebo (vehicle). The treatment duration was 4 months. Primary efficacy outcomes were the number of attacks per month, and the number of patients with a mean of <1 attack per month. Quality of life was assessed using a 0-10-grade visual analog scale (VAS), and safety was assessed according to the number and severity of adverse events.
  
  
  
  Twenty-five patients with colchicine-resistant FMF (14 women) were enrolled, of whom 12 were randomized to receive anakinra and 13 to receive placebo. The mean ± SD number of attacks per patient per month was 1.7 ± 1.7 in those receiving anakinra and 3.5 ± 1.9 in those receiving placebo (P = 0.037). Six patients in the anakinra group, compared to none in the placebo group, had <1 attack per month (P = 0.005). A beneficial effect of anakinra was noted in the number of attacks in the joints per month in patients receiving anakinra (mean ± SD 0.8 ± 1.6 versus 2.1 ± 1.1 in the placebo group; P = 0.019) and in quality of life (mean ± SD VAS score 7.7 ± 2.3 in the anakinra group versus 4.2 ± 2.9 in the placebo group; P = 0.045). The number of adverse events per patient per month was comparable between the anakinra group and the placebo group (mean ± SD 2.03 ± 1.75 versus 3.34 ± 2.5; P = 0.22). There were no severe adverse events.
  
  
  
  In this randomized controlled trial, anakinra appears to be an effective and safe treatment for colchicine-resistant FMF.
authors.affiliation: Sheba Medical Center, Ramat Gan, Israel, and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Ben-Zvi
authors.affiliation: Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Kukuy
authors.affiliation: Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Eitan
authors.initials: E
authors.lastname: Giat
authors.affiliation: Sheba Medical Center, Ramat Gan, Israel, and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Elon
authors.initials: E
authors.lastname: Pras
authors.affiliation: Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Feld
authors.affiliation: Sheba Medical Center, Ramat Gan, Israel, and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Shaye
authors.initials: S
authors.lastname: Kivity
authors.affiliation: Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Oleg
authors.initials: O
authors.lastname: Perski
authors.affiliation: Sheba Medical Center, Ramat Gan, Israel, and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Bornstein
authors.affiliation: Sheba Medical Center, Ramat Gan, Israel, and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Chagai
authors.initials: C
authors.lastname: Grossman
authors.affiliation: Medistat, Ltd., Tel Aviv, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Harari
authors.affiliation: Sheba Medical Center, Ramat Gan, Israel, and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Merav
authors.initials: M
authors.lastname: Lidar
authors.affiliation: Sheba Medical Center, Ramat Gan, Israel, and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Avi
authors.initials: A
authors.lastname: Livneh
mesh_terms: D000328:Adult; D003078:Colchicine / Q000627:therapeutic use; D004311:Double-Blind Method; D004351:Drug Resistance; D010505:Familial Mediterranean Fever / Q000188:drug therapy*; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D008297:Male; D011788:Quality of Life
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D003078:Colchicine