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.
N/ACitations
Citations of this article
6Readers
Mendeley users who have this article in their library.

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.

Cite

CITATION STYLE

APA

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

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free