Rheumatoid Arthritis Induction Trial (RAITMAT)

描述（由申请人提供）：最近的数据支持在大量接受联合治疗的RA患者中诱导缓解的可能性；这些数据支持了“类风湿关节炎诱导试验与甲氨蝶呤和抗肿瘤坏死因子治疗（RAITMAT）研究”的需要和设计。我们的假设是，早期类风湿关节炎（RA）患者在接受甲氨蝶呤、抗肿瘤坏死因子（anti-TNF）和口服皮质类固醇联合治疗后，50%的受试者在12个月时能够缓解，并且50%的受试者在盲法停用抗肿瘤坏死因子后至少12个月仍处于缓解状态。这项重要的研究将建立最具成本效益的方法来管理早期RA患者，同时避免中期关节损伤，残疾和失业。抗肿瘤坏死因子免费假期也可以减少严重的不良事件，如感染。此外，我们将提出最先进的机制研究，这将为研究疾病及其在受试者之间的可变性提供框架，以及潜在的生物标志物，这些生物标志物可能有助于预测对这种诱导治疗的反应（或缺乏反应）。一个由临床试验学家、生物统计学家和基础研究人员组成的指导委员会已经成立，以设计RAITMAT试验。临床试验计划拨款需要用于以下具体目的：1.)主持指导委员会的会议和电话会议，以撰写资助RAITMAT试验所需的拨款；2)。制定研究资料，如操作和程序手册、质量控制程序、知情同意原型和数据收集工具；3)。从制药/生物技术公司获得研究药物；和4)。完成要进行的机械研究。该提案汇集了一组经验丰富的研究人员参与类风湿关节炎的研究。我们将前瞻性地分析对RA联合治疗反应的分子特征，以诱导缓解。这些研究的结果将为早期侵袭性类风湿性关节炎患者的最佳治疗方法提供新的信息。拟议试验的一个重要目标是确定蛋白质组学和/或基因组生物标志物，以指导患者选择和治疗。评估的技术包括自身抗体、细胞因子、mRNA和其他生物标志物分析技术。该项目旨在收集知识专长，以制定机制和方案，通过评估机制研究和潜在的生物标志物，以证明在类风湿关节炎早期积极干预过程中使用的强效治疗方案的短期益处。这将导致拟议的类风湿关节炎诱导试验与MTX和抗肿瘤坏死因子治疗（RAITMAT）的发展。

DESCRIPTION (provided by applicant): Recent data support the possibility of inducing a remission in a large number of RA patients receiving combination therapy; this data supports the need and the design of this "Rheumatoid Arthritis Induction Trial with methotrexate and anti-TNF therapy (RAITMAT) study. Our hypothesis is that patients with early rheumatoid arthritis (RA) when treated with a combination of methotrexate, anti-tumor necrosis factor (anti-TNF) agent and oral corticosteroids will be able to induce a remission in 50% of subjects at 12 months, and that 50% there subjects will remain in remission at least 12 months after discontinuing the anti-TNF agent in a blinded manner. This important study will establish the most cost effective ways to manage early RA patients, while avoiding intermediate-term joint damage, disability and unemployment. The anti-TNF free holidays may also minimize serious adverse events, such as infections. In addition, we will propose state of the art mechanistic studies that will provide the framework for studying the disease and its variability among subjects, as well as potential biomarkers that might be useful to predict response (or lack of response) to this induction therapy. A steering committee of clinical trialists, biostatisticians, and basic researchers has been formed to design the RAITMAT trial. A clinical trials planning grant is needed for the following specific aims: 1.) Conduct meetings and teleconferences of the steering committee to write the grants needed for funding of the RAITMAT trial; 2.) Develop study materials such as manual of operations & procedures, quality control procedures, informed consent prototype, and data collection instruments; 3.) Secure study medications from pharmaceutical/biotech companies; and 4.) Finalize mechanistic studies to be performed. This proposal brings together an experienced group of investigators involved with RA research. We will prospectively analyze the molecular signatures of responses to treatment with combinations of RA therapies that will induce remission. The results of these studies will provide novel information on best treatment approaches in patients with early aggressive RA. An important objective of the proposed trial will be to identify proteomic and/or genomic biomarkers to guide patient selection and therapy. Technologies to be evaluated include autoantibody, cytokine, mRNA, and other biomarker profiling technologies. This project seeks to gather intellectual expertise to develop mechanism and protocol by which to evaluate mechanistic studies and potential biomarkers for evidence of the short term benefits of powerful treatment regimens used in the course of early aggressive intervention of rheumatoid arthritis. This will lead to the development of the proposed Rheumatoid Arthritis Induction Trial with MTX and Anti-TNF Therapy (RAITMAT).