Strategies for Evaluating and Treating Early Synovitis

描述(由申请人提供)：本次申请高风险风湿性、肌肉骨骼和皮肤病研究基金的目的是开发一种研究早期滑膜炎的策略，并提供一个框架来测试治疗类风湿性关节炎(RA)的机会窗假说。RA是一种慢性炎症性关节炎，可导致畸形和残疾。在治疗类风湿性关节炎的药物中，DMARDS(疾病修饰抗风湿药物)可以改善关节炎的体征和症状，防止或减缓导致畸形的软骨和骨骼的破坏。由于DMARDS的早期治疗改善了临床结果，因此有充分的理由在病程早期使用这些药物。然而，这种早期应用因诊断的不确定性而变得复杂，包括难以区分类风湿关节炎患者和非类风湿关节炎患者，以及早期疾病缓解的发生。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及早开始DMARDS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评估机会窗假说的临床试验。这一假说表明，在疾病早期积极治疗滑膜炎可以防止类风湿性关节炎或其他持续性滑膜炎的出现。目前，国内和国际上都对开展这样一项试验以及它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，这项高风险赠款将解决招募和识别早期疾病患者方面的基本问题，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测试机会之窗假说；2)在先导研究中测试患者招募；以及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.