Abatacept Vs TNF Blockade in Early Rheumatoid Arthritis

描述(申请人提供)：虽然类风湿性关节炎(RA)的治疗已经取得了相当大的进展，但只有少数接受了疾病修改的抗风湿药物的最佳方案治疗的患者实现了临床缓解。达到临床缓解是治疗的理想目标，因为它与关节破坏的最小或没有放射学进展有关。为此，我们建议进行一项随机、双盲、安慰剂对照的早期类风湿关节炎试验，比较甲氨蝶呤(MTX)联合阿巴坦治疗后的缓解率与MTX和抗肿瘤坏死因子(TNF)抑制剂治疗后的缓解率。拟议的研究设计包括一个新的停药阶段，在此期间，达到最低水平疾病活动的患者将停止他们分配的治疗，即阿巴塔塞普或肿瘤坏死因子抑制剂，并再跟踪9个月，以评估持续的临床缓解。我们建议将一些机制研究整合到试验中，旨在识别治疗反应的预后生物标志物。要实现这种综合研究战略的宏伟目标，将需要一个为期12个月的密集规划阶段，这是拟议项目的重点。该项目将由E·威廉·圣克莱尔博士领导，他是一位经验丰富的临床研究员，在治疗类风湿性关节炎方面具有专业知识。规划阶段的目标如下：1)有效地利用疾病专家指导委员会和杜克临床研究所的资产来开发最佳的临床试验设计，并指导方案开发的其他重要阶段；2)开发使用各种单一和多重分析平台来识别治疗反应的生物标记物的研究战略；以及3)与免疫耐受网络发展有效的合作，以获得他们的多重分析平台，包括RNA表达阵列和高通量流式细胞术，以及实现特定目标2的目标的分析工具。对此规划阶段的支持将使我们能够产生临床方案开发的关键交付成果，一套高度集成的创新生物标记物研究，以及用于试验实施的强大基础设施，总体目标是向NIAMS提交一份优秀的申请，为拟议的临床试验提供资金。治疗类风湿性关节炎(RA)的下一个主要步骤是针对人们独特的基因构成和其他因素而设计的缓解疗法。研究已经表明，这种疗法可以造福公众健康。这项拟议的临床试验将比较两种新疗法对早期RA的缓解诱导能力，并寻找预测治疗反应的生物标志物。

DESCRIPTION (provided by applicant): While considerable progress has been made in the treatment of rheumatoid arthritis (RA), only a minority of patients treated with optimal regimens of disease-modifying anti-rheumatic drugs achieve a clinical remission. Achieving a clinical remission is a desired goal of therapy because it is associated with minimal or no radiographic progression of joint destruction. To this end, we are proposing a randomized, double-blind, placebo-controlled trial in early RA comparing remission rates obtained following treatment with methotrexate (MTX) plus abatacept versus MTX and an anti-tumor necrosis factor (TNF) inhibitor. The proposed study design includes a novel withdrawal phase during which patients achieving a minimal level of disease activity will discontinue their assigned treatment, namely abatacept or a TNF inhibitor, and be followed for an additional 9 months to evaluate for sustained clinical remission. We propose to integrate a number of mechanistic studies into the trial aimed at identifying prognostic biomarkers of treatment response. To achieve the ambitious aims of such a comprehensive research strategy will require an intensive 12-month planning phase, which is the focus of the proposed project. The project will be led by Dr. E. William St.Clair, an experienced clinical investigator with expertise in the treatment of RA. The aims of the planning phase are as follows: 1) To effectively utilize a Steering Committee of disease experts and the assets of the Duke Clinical Research Institute to develop an optimal clinical trial design and guide other important phases of protocol development; 2) To develop a research strategy for identifying biomarkers of treatment response using a variety of uniplex and multiplex assay platforms; and 3) To develop an effective collaboration with the Immune Tolerance Network to obtain access to their multiplex assay platforms, including RNA expression arrays and high throughput flow cytometry, as well as analytical tools to implement the goals of specific aim 2. The support for this planning phase will enable us to produce the key deliverables of clinical protocol development, a highly integrated set of innovative biomarker studies, and a robust infrastructure for trial implementation, with the overall goal of submitting an outstanding application to NIAMS for funding of the proposed clinical trial. Therapies designed to achieve remission and tailored for people's distinct genetic make-up and other factors are the next major steps in the management of rheumatoid arthritis (RA). Research has already shown that such therapies can benefit public health. The proposed clinical trial will compare the remission-inducing capabilities of two novel therapies for early RA, and search for biomarkers that predict treatment response.