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

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-1 alpha, IL-1 beta, IL-1Ra and serum hyaluronan (HA), an indicator of synovial inflammation. The primary outcome, standardized Knee Injury and Osteoarthritis Outcome Score (MOOS) 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 (MOOS 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 MOOS P < 0.0001). There were no adverse reactions in either group. SF IL-1 alpha (P = 0.05) and serum HA (P = 0.03), but not IL-1 beta, or IL-1Ra, decreased significantly in the IL-1Ra but not the placebo treated patients. Compared with placebo. IL-1 alpha 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. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.