007 INTRAARTICULAR IL1-RA AFTER ACUTE KNEE INJURY DECREASES BIOMARKERS OF INFLAMMATION AND IMPROVES PAIN AND FUNCTION

  • Byers Kraus V
  • Birmingham J
  • Stabler T
  • et al.
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Abstract

Purpose: This pilot study evaluated the clinical therapeutic benefits of intraarticular IL-1 receptor antagonist (IL-1Ra) delivered during the first month after severe acute knee injury with anterior cruciate ligament (ACL) tear. Methods: Patients: This study was approved by the Institutional Review Board and performed under a waiver of IND from the FDA. A total of 11 patients were treated within the first 30 days of acute knee injury: 6 patients were randomized to intra-articular IL-1Ra (anakinra 150 mg intra-articular) and 5 patients to saline placebo (equal volume 1 ml intraarticular). Patients were recruited a mean 15+/-7 (SD) days from knee injury (range 6-27 days). The mean age of participants was 24+/-4 (SD) years, (6 male, 5 female; 2 African American). Enrollment was limited to patients under 40 years of age to try to insure the lack of underlying pre-existing arthropathy. Clinical knee MRIs were performed revealing isolated anterior cruciate ligament (ACL) tear (partial or full) in all patients: 3 patients with isolated ACL tear; 3 patients with medial collateral ligament and ACL tears; 4 patients with meniscal and ACL tears; and 1 patient with medial collateral ligament, meniscal, and ACL tears. Biomarker Assays: Samples of synovial fluid (n=9 patients) and serum (all patients) were available at baseline (prior to injection) and day 28 samples (prior to surgery) and analyzed for IL-1alpha, IL-1beta, and IL-1Ra, using commercial immunoassays (R&D Quantikine sandwich assays; intra- and inter-assay CVs were <10%). Serum levels of hyaluronan (HA), associated with joint inflammation, were quantified using a commercially available (Table Presented) immunoassay (Corgenix; intra- and inter-assay CVs were 2% and 3% respectively). Functional Outcomes: The standardized KOOS questionnaire was obtained at baseline (0), 4 days, 14 days, and 28 days or the day of surgery. Statistical Analysis: The Wilcoxon rank sum test was used to evaluate the change in KOOS from baseline to follow-up within a treatment group. Two-tailed t-test was used to compare the change scores (pre-post synovial fluid concentrations) between placebo and drug treated groups. Results: As shown in the table, the Anakinra group had substantially greater improvement (~1-3 s.d.) in key outcomes whereas the placebo group had much less improvement (~1/4 of s.d. on most outcomes). Statistically significant improvements in KOOS pain (p=0.04) and function (activities of daily living, p=0.03), and total KOOS (p=0.03) were observed in response to IL1-Ra, but not placebo. In the anakinra treated group this corresponded to reductions in Pain of 23%, improvement in Activities of Daily Living of 46%, and improvement in total KOOS of 24%; in contrast, the placebo group changed only 4%, 6% and 7% for these outcomes respectively. There were no adverse reactions in either the anakinra or saline placebo treated groups. Synovial fluid IL-1alpha, IL-1beta, and IL-1Ra concentrations exceeded serum concentrations. IL-1alpha increased in all the placebo treated patients whereas it decreased in 4 of 5 of the anakinra treated patients (p=0.05). Although IL-1 and IL-1Ra declined dramatically over time post injury, there was no significant difference based on treatment. Serum HA decreased in all the anakinra treated patients (n=6 pairs) from Time 1 to Time 2 (p=0.03) while the change in the placebo treated patients was not significant. Conclusions: IL-1Ra decreased pain and improved function in our randomized pilot trial of acute knee injury. The decreases in serum HA and synovial fluid IL-1alpha in the IL-1Ra treated patients are consistent with a decrease in synovial inflammation in acute knee injury in response to IL-1Ra therapy.

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Byers Kraus, V., Birmingham, J., Stabler, T., Feng, S., Taylor, D. C., Moorman, C. T., … Toth, A. (2010). 007 INTRAARTICULAR IL1-RA AFTER ACUTE KNEE INJURY DECREASES BIOMARKERS OF INFLAMMATION AND IMPROVES PAIN AND FUNCTION. Osteoarthritis and Cartilage, 18, S11–S12. https://doi.org/10.1016/s1063-4584(10)60034-9

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