TUMOR NECROSIS FACTOR-ALPHA INHIBITION (ADALIMUMAB) IN OSTEOARTHRITIS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 骨关节炎（OA）影响超过7000万美国人，是导致我们老龄化人口残疾的主要因素。 OA是一种异质性疾病，与关节软骨的完整性缺陷和底层骨的变化相关。 虽然OA的进展通常被认为主要是退行性而不是炎症过程，但有大量越来越多的证据支持关键炎症介质在这种疾病中的作用。细胞因子是炎性关节疾病（包括OA）的重要介质，并参与这种疾病中软骨和骨中分解代谢和降解事件的恶性循环的启动和持续。 据推测，针对促炎细胞因子肿瘤坏死因子-α（TNF-α）的治疗可能导致疾病的显著临床改善。 本初步研究的目的是建立TNF阻滞剂治疗骨关节炎的安全性和临床疗效的初步数据。 这项为期12周的双盲安慰剂对照试验的主要终点将是根据美国风湿病学会（ACR）应答者指数（ACR 20）实现20%临床改善的患者比例。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Osteoarthritis (OA) affects over 70 million Americans and is a major factor contributing to disability in our aging population. OA is heterogeneous condition associated with defective integrity of articular cartilage and changes in underlying bone. Although the progression of OA is generally considered to be predominantly a degenerative rather than an inflammatory process, there is a substantial, growing body of evidence supporting a role for key inflammatory mediators in this condition. Cytokines are important mediators of inflammatory joint diseases including OA, and are involved in the initiation and perpetuation of a vicious cycle of catabolic and degradative events in cartilage and bone in this illness. It is hypothesized that treatment directed against the pro-inflammatory cytokine Tumor Necrosis Factor-alpha (TNF-alpha) could lead to significant clinical improvements in the disease. The objective of this pilot study is to establish preliminary data on the safety and clinical efficacy of TNF blockade in osteoarthritis. The primary endpoint of this 12-week double-blind placebo controlled trial will be the proportion of patients achieving a 20% clinical improvement based on the American College of Rheumatology (ACR) responder index (ACR20).