Zachary S. Aman, B.A., Nicholas N. DePhillipo, Ph.D., A.T.C., Filippo Familiari, M.D., LTC Jonathan F. Dickens, M.D., Robert F. LaPrade, M.D., Ph.D., and Maj. Travis J. Dekker, M.D.
To evaluate the efficacy of selective interleukin (IL)-1 inhibitor therapy in the reduction of posttraumatic osteoarthritis (PTOA) progression following knee ligament or meniscal injury. Methods: A systematic review was conducted evaluating the disease-modifying efficacy of selective IL-1 inhibition in the setting of knee PTOA. Results: The literature search identified 364 articles and 11 studies were included (n ¼ 10 preclinical, n ¼ 1 clinical). Drug delivery in
preclinical studies was administered using IL-1Raeencoded helper-dependent adenovirus particles (n ¼ 3), synovial cells transfected with an IL-1Raeencoded retroviral vector (n ¼ 3), or varying chemical compositions of nonviral microcapsule gene carriers (n ¼ 4). Intervention with selective IL-1 inhibitor therapy within 2 weeks of injury provided the greatest protective benefits in reducing the progression of PTOA regardless of drug delivery methodology in preclinical models. The majority of studies reported significantly better cartilage integrity and reduction in lesion size in animals treated with gene therapy with the greatest effects seen in those treated within 5 to 7 days of injury. Conclusions: Early intervention with selective IL-1 inhibitor therapy were effective in reducing proinflammatory IL-1b levels in the acute and subacute phases following traumatic knee injury in preclinical animal model studies, while significantly reducing cartilage damage, lesion size, and PTOA progression at short-term follow-up. However, it was found that the effect of these therapies diminished over time. Clinical Relevance: Acute, intra-articular injection of selective IL-1 inhibitors may reduce PTOA progression, supporting the need for additional basic and clinical investigation.
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