title: Effects of intraarticular IL1-Ra for acute anterior cruciate ligament knee injury: a randomized controlled pilot trial (NCT00332254).
abstract: OBJECTIVE
  To evaluate the clinical effectiveness of intraarticular IL-1 receptor antagonist (IL-1Ra) for anterior cruciate ligament (ACL) tear.
  
  
  METHODS
  Eleven patients with acute ACL tear confirmed by magnetic resonance imaging (MRI) were randomized to receive a single intraarticular injection of IL-1Ra (anakinra 150 mg, n = 6) or equal volume of saline placebo (1 ml, n = 5). The double-blinded treatment was administered a mean 2 weeks after injury. Synovial fluid (SF) (n = 9 patients) and sera (all patients) were available at baseline (prior to injection) and immediately prior to surgery (mean 35 days later) and analyzed for SF IL-1α, IL-1β, IL-1Ra and serum hyaluronan (HA), an indicator of synovial inflammation. The primary outcome, standardized Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, was obtained at 0 (baseline), 4, and 14 days after injection.
  
  
  RESULTS
  Compared with placebo, the IL-1Ra group had substantially greater improvement in key outcomes over 14 days (KOOS pain P = 0.001; activities of daily living P = 0.0015; KOOS sports function P = 0.0026; KOOS quality of life (QOL) P = 0.0048; and total KOOS P < 0.0001). There were no adverse reactions in either group. SF IL-1α (P = 0.05) and serum HA (P = 0.03), but not IL-1β, or IL-1Ra, decreased significantly in the IL-1Ra but not the placebo treated patients. Compared with placebo, IL-1α was borderline significantly different in the IL-1Ra treated group (P = 0.06).
  
  
  CONCLUSIONS
  Administered within the first month following severe knee injury, IL-1Ra reduced knee pain and improved function over a 2-week interval. This promising proof of concept study provides a new paradigm for studies of acute joint injury and suggests that a larger follow-up study is warranted.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. vbk@duke.edu
authors.forename: V B
authors.initials: VB
authors.lastname: Kraus
authors.forename: J
authors.initials: J
authors.lastname: Birmingham
authors.forename: T V
authors.initials: TV
authors.lastname: Stabler
authors.forename: S
authors.initials: S
authors.lastname: Feng
authors.forename: D C
authors.initials: DC
authors.lastname: Taylor
authors.forename: C T
authors.initials: CT
authors.lastname: Moorman
authors.forename: W E
authors.initials: WE
authors.lastname: Garrett
authors.forename: A P
authors.initials: AP
authors.lastname: Toth
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D000070598:Anterior Cruciate Ligament Injuries; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000627:therapeutic use*; D007718:Knee Injuries / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000534:rehabilitation; D008279:Magnetic Resonance Imaging; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D010865:Pilot Projects; D011788:Quality of Life; D020127:Recovery of Function; D013582:Synovial Fluid / Q000378:metabolism; D015599:Trauma Severity Indices; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein