Intra-articular Anakinra for the Treatment of Persistent Inflammation and Arthrofibrosis following Anterior Cruciate Ligament Reconstruction

Abstract

Purpose: Postoperative inflammation and arthrofibrosis remain difficult problems following ACL reconstruction. Interleukin-1 (IL-1) is a potent driver of intra-articular inflammation and arthrofibrosis following injury and surgery. Anakinra (Kineret, Amgen, Thousand Oaks, CA) is an IL-1 receptor antagonist. We hypothesize that postoperative intra-articular anakinra use decreases inflammation and subsequent arthrofibrosis, reducing the need for arthroscopic debridement and manipulation under anesthesia.Methods: Four patients (ages 15-56) who were treated with anakinra for persistent postoperative inflammation and scarring within 4 months of ACL reconstruction were retrospectively reviewed. Anakinra was utilized when patients were unable to obtain full extension and at least 90° of flexion 1 month postoperatively in association with persistent effusions or decreased patellar mobility.Results: Anakinra injection was performed between 36 and 97 days postsurgery. All four reported improvements in range of motion and decreased pain and effusions within 10 days of injection. One patient, who did not receive anakinra until more than 3 months postsurgery, required eventual arthroscopic debridement of a cyclops lesion but none of the patients required frank lysis of adhesions or manipulation under anesthesia. No adverse reactions to anakinra occurred. Conclusion:Based on previous experience, we believe that all of these patients would have required arthroscopic debridement of scar tissue and manipulation under anesthesia to regain motion were not for the anakinra treatment. Clearly, the concept of IL-1 inhibition in the postoperative knee requires further research, but early results are promising for this unique treatment of a difficult clinical problem.

Formation process of joint contracture after anterior cruciate ligament reconstruction in rats

“…In patients with arthrofibrosis after ACLR, intra-articular injection of the IL-1 antagonist anakinra improved the ROM. 15 Fibroblasts produce extracellular matrix and their proliferation is an important process in the formation of arthrofibrosis. 33,34 Fibroblasts isolated from the synovium express high levels of the IL-1 receptor 35 and proliferate in response to IL-1β.…”

“…12 Previous studies suggested that postsurgery inflammation triggers the formation of arthrofibrosis, 11,13 and antiinflammatory treatments with corticosteroids or interleukin-1 (IL-1) receptor antagonists improved the range of motion (ROM) in patients with ACLR-induced arthrofibrosis. 14,15 However, the details of the formation processes of arthrofibrosis are unknown. Elucidation of the time-dependent changes in inflammatory and fibrotic reactions after ACLR will help to guide the optimal timing of antiinflammatory/antifibrotic treatments.…”