Effects of intraarticular IL1-Ra for acute anterior cruciate ligament knee injury: a randomized controlled pilot trial (NCT00332254)

Osteoarthritis Cartilage. 2012 Apr;20(4):271-8. doi: 10.1016/j.joca.2011.12.009. Epub 2012 Jan 10.


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.

Trial registration: ClinicalTrials.gov NCT00332254.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Adult
  • Anterior Cruciate Ligament Injuries*
  • Biomarkers / metabolism
  • Female
  • Humans
  • Injections, Intra-Articular
  • Interleukin 1 Receptor Antagonist Protein / administration & dosage
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Knee Injuries / complications
  • Knee Injuries / diagnosis
  • Knee Injuries / drug therapy*
  • Knee Injuries / rehabilitation
  • Magnetic Resonance Imaging
  • Male
  • Pain / drug therapy
  • Pain / etiology
  • Pilot Projects
  • Quality of Life
  • Recovery of Function
  • Synovial Fluid / metabolism
  • Trauma Severity Indices
  • Treatment Outcome
  • Young Adult


  • Biomarkers
  • Interleukin 1 Receptor Antagonist Protein

Associated data

  • ClinicalTrials.gov/NCT00332254