Strategies for Evaluating and Treating Early Synovitis

描述（由申请人提供）：本申请的高风险风湿性和肌肉骨骼和皮肤疾病研究资助的目标是制定研究早期滑膜炎的策略，并提供一个框架来测试类风湿性关节炎（RA）治疗中的机会窗口假说。RA是一种慢性炎症性关节炎，可导致畸形和残疾。在治疗类风湿关节炎的药物中，DMARDs（疾病修饰抗风湿药物）可以改善关节炎的体征和症状，预防或减缓导致畸形的软骨和骨骼破坏。由于早期使用DMARDs治疗可改善临床结局，因此在病程早期使用这些药物有很强的理由。然而，这种早期使用是复杂的诊断不确定性，包括在区分RA患者与RA以外的炎性关节病以及在早期疾病的缓解的发生的困难。此外，早期治疗的努力可能会受到患者寻求治疗的延迟以及提供者的不确定性或不愿意早期开始DMARD的限制。这些问题的解决最好是在一个全面的临床研究计划的背景下完成，该计划最终将包括一项临床试验，以评估机会之窗假设。这一假说指出，在疾病早期对滑膜炎进行积极治疗可能会预防RA或其他持续性滑膜炎的出现。目前，各国和国际社会都对开展这一试验及其为解决疾病发病机制中的关键问题提供的机会感兴趣。因此，这一高风险赠款将解决招募和识别早期疾病患者的基本问题，并为临床试验奠定基础。提出了三个具体目标：1）开发一项临床试验来检验机会窗口假说; 2）在试点研究中检验患者招募情况; 3）评估早期干预的伦理问题。

DESCRIPTION (provided by applicant): The goal of this application for a High Risk Rheumatic and Musculoskeletal and Skin Diseases Research grant is to develop a strategy for studying early synovitis and provide a framework to test the window-of-opportunity hypothesis in the treatment of rheumatoid arthritis (RA). RA is a chronic inflammatory arthritis that can lead to deformity and disability. Among drugs to treat RA, DMARDs (disease modifying anti-rheumatic drugs) can improve the signs and symptoms of arthritis and prevent or slow the destruction of cartilage and bone that leads to deformity. Since early treatment with DMARDs improves clinical outcomes, there is a strong rationale for instituting these agents early in the course of disease. Such early use, however, is complicated by diagnostic uncertainty, including the difficulties in differentiating patients with RA from those with inflammatory arthropathies other than RA as well as the occurrence of remission in early disease. Furthermore, efforts to institute therapy early may be limited by delays in patients seeking care as welt as provider uncertainty or reluctance to begin DMARDs early. Resolution of these issues can be best accomplished in the context of a comprehensive program of clinical research that will ultimately include a clinical trial to assess the window-of-opportunity hypothesis. This hypothesis states that the aggressive treatment of synovitis early in disease may prevent the emergence of RA or other persistent synovitis. At present, there is national and international interest in the conduct of such a trial and the opportunities it provides for addressing critical issues in disease pathogenesis. This high-risk grant will therefore address fundamental questions in the recruitment and identification of patients with early disease and establish the basis for a clinical trial. Three specific aims are proposed: 1) to develop a clinical trial to test the window-of-opportunity hypothesis; 2) to test recruitment of patients in a pilot study; and 3) to assess ethical issues of early intervention.