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

• Published in: Osteoarthritis and cartilage Vol. 20; no. 4; pp. 271 - 278
• Main Authors: Kraus, V.B, Birmingham, J, Stabler, T.V, Feng, S, Taylor, D.C, Moorman, C.T, Garrett, W.E, Toth, A.P
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2012
• Subjects: Activities of Daily Living; Adult; Anterior cruciate ligament; Anterior Cruciate Ligament Injuries; Biomarkers; Biomarkers - metabolism; Clinical trial; Female; Humans; IL-1Ra; Injections, Intra-Articular; Interleukin 1 Receptor Antagonist Protein - administration & dosage; Interleukin 1 Receptor Antagonist Protein - therapeutic use; Joint injury; Knee Injuries - complications; Knee Injuries - diagnosis; Knee Injuries - drug therapy; Knee Injuries - rehabilitation; Magnetic Resonance Imaging; Male; Pain - drug therapy; Pain - etiology; Pilot Projects; Post-traumatic arthritis; Quality of Life; Recovery of Function; Rheumatology; Synovial Fluid - metabolism; Trauma Severity Indices; Treatment Outcome; Young Adult; Biomarkers; Post-traumatic arthritis; Clinical trial; Joint injury; IL-1Ra; Anterior cruciate ligament
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2011.12.009

Summary 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.