title: Intraarticular injection of anakinra in osteoarthritis of the knee: a multicenter, randomized, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  To evaluate the clinical response, safety, and tolerability of a single intraarticular injection of anakinra in patients with symptomatic osteoarthritis (OA) of the knee.
  
  
  METHODS
  Patients with OA of the knee were enrolled in a multicenter, double-blind, placebo-controlled study and randomized 2:1:2 to receive a single intraarticular injection of placebo, anakinra 50 mg, or anakinra 150 mg in their symptomatic knee. Patients were evaluated for 12 weeks postinjection. The primary end point was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline to week 4. Safety assessments included the evaluation of adverse events (AEs), laboratory tests, and vital signs. Pharmacokinetic parameters were assessed in a subset of patients.
  
  
  RESULTS
  Of 170 patients who enrolled, 160 (94%) completed the study. The mean improvements from baseline to week 4 in the WOMAC score were not statistically different between the placebo group and the patients who received 50 mg of anakinra (P = 0.67) or 150 mg of anakinra (P = 0.77). Anakinra was well tolerated. No withdrawals due to AEs or serious AEs, and no serious infections or deaths were reported. No clinically significant trends were noted in laboratory values or vital signs. Pharmacokinetic parameters demonstrated that the mean terminal half-life of anakinra in serum after intraarticular injection was approximately 4 hours.
  
  
  CONCLUSIONS
  Anakinra was well tolerated as a single 50-mg or 150-mg intraarticular injection in patients with OA of the knee. However, anakinra was not associated with improvements in OA symptoms compared with placebo.
authors.affiliation: Department of Rheumatology, Hospital Henri Mondor, University Paris XII, Créteil, France. xavier.chevalier@hmn.ap-hop-paris.fr
authors.forename: X
authors.initials: X
authors.lastname: Chevalier
authors.forename: P
authors.initials: P
authors.lastname: Goupille
authors.forename: A D
authors.initials: AD
authors.lastname: Beaulieu
authors.forename: F X
authors.initials: FX
authors.lastname: Burch
authors.forename: W G
authors.initials: WG
authors.lastname: Bensen
authors.forename: T
authors.initials: T
authors.lastname: Conrozier
authors.forename: D
authors.initials: D
authors.lastname: Loeuille
authors.forename: A J
authors.initials: AJ
authors.lastname: Kivitz
authors.forename: D
authors.initials: D
authors.lastname: Silver
authors.forename: B E
authors.initials: BE
authors.lastname: Appleton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D012720:Severity of Illness Index
chemical_list: D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein