Treat to Target to Reduce Atherosclerosis in Rheumatoid Arthritis

描述(由申请人提供)：多项流行病学研究表明，类风湿性关节炎(RA)中心血管疾病(CVD)的风险增加；它是RA的头号死亡原因。许多观察性研究支持积极免疫抑制对心血管疾病风险的益处，认为类风湿关节炎炎症负担的增加是导致这种风险的原因之一。然而，关于治疗对心血管疾病风险的影响，观察性研究之间存在相互矛盾的发现，重要的是，没有一项研究提供足够的证据基础来告知提供者如何管理这种风险。目前，人们普遍热衷于使用靶向治疗(TTT)来管理RA的关节体征和症状。然而，没有数据表明TTT是否可以改善非关节结局，如动脉粥样硬化。这项建议描述了一项随机对照试验的原理和设计，该试验测试TTT与常规护理对颈动脉厚度(IMT)进展和其他动脉粥样硬化进展的次要指标的影响。我们要求24个月的资金来进一步计划这项试验。规划期将涉及许多活动，包括选择核心血管实验室、确定最佳成像方案、编写成像培训材料、最后确定试验设计和程序、编写操作程序手册以及场地招聘/选择。我们预计在第二年早些时候提交试验方案，然后继续进行IRB工作、现场分包和创建试验材料。这将使我们能够在试用期早期做好招聘准备。该试验将是类风湿性关节炎的首个此类试验，并将为类风湿性关节炎患者心血管风险的管理提供重要的临床信息。

DESCRIPTION (provided by applicant): Multiple epidemiologic studies have demonstrated an increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA); it is the number one cause of death in RA. The elevated inflammatory burden of RA is postulated to contribute to this risk, supported by a number of observational studies supporting the benefits of aggressive immunosuppression on CVD risk. However, there are conflicting findings among the observational studies regarding the effect of treatment on CVD risk, and, importantly, none provides a sufficient evidence-base to inform providers how to manage this risk. Currently, there is general enthusiasm regarding Treat to Target (TTT) in RA for managing articular signs and symptoms. However, there are no data whether TTT may improve non-articular outcomes, such as atherosclerosis. This proposal describes the rationale and design of a randomized controlled trial testing the effects of TTT versus usual care on the progression of carotid thickness (IMT) and other secondary measures of atherosclerosis progression. We request 24 months of funding to further plan this trial. The planning period will entail many activities, including selecting a core vascular laboratory, determining the best imaging protocol, developing training materials for the imaging, finalizing trial design and procedures, developing a Manual of Operating Procedures, and site recruitment/selection. We anticipate submission of a trial proposal early during year 2 and then continuing with IRB work, site subcontracting, and creating trial materials. This will allow us to be ready to recruit early in the trial period. Thetrial will be the first of its kind in RA and will provide important clinical information for the management of CV risk in RA patients.