Inflammation and cardiovascular disease in RA

描述(申请人提供)：类风湿性关节炎(RA)是一种慢性、进行性、全身性、炎症性疾病，主要攻击周围关节和周围的肌腱和韧带。这种通常非常痛苦和虚弱的疾病影响着大约130万美国人，其中约70%是女性。10%的受影响受试者患有完全残疾。在过去的十年里，类风湿性关节炎(RA)的治疗取得了长足的进步。使用拮抗肿瘤坏死因子的生物制剂已导致发病率的降低以及临床上有意义的生活质量的改善。然而，相当大比例的RA患者，在临床试验中，从20%到50%不等，对这些药物未能产生强烈的临床反应。考虑到与肿瘤坏死因子拮抗剂相关的昂贵的费用和潜在的严重毒副作用，识别肿瘤坏死因子拮抗剂治疗反应的预测因素将有助于优化类风湿关节炎患者的临床治疗。新的光学层析成像(OTI)方法是近年来发展起来的，目前已被用于从乳腺癌成像到脑活动成像的各种临床应用。这项新技术有望在不使用电离辐射的情况下，以相对较低的成本为各种疾病过程提供新的见解。Hielscher博士的研究小组最近表明，OTI对受RA影响的手指关节的微小变化特别敏感。这些变化表现为关节内的光吸收和散射系数的差异，这是由于关节周围滑液和血管系统的光学性质的变化造成的。我们假设，光学断层成像(OTI)方法将能够在开始治疗的最初几个月甚至几周内检测到使用肿瘤坏死因子拮抗剂治疗的关节炎关节中发生的变化。因此，这一修订应用的具体目标是对20名RA患者进行纵向观察性先导研究，以确定可用于预测治疗结果的光学成像生物标记物。特别是，我们预计对治疗有反应的患者将表现出跨越关节的散射和吸收系数的变化增加。此外，吸收系数和散射系数都会减小。对于没有观察到治疗反应的患者，在治疗过程中不会观察到任何变化。一项成功的研究将为新成立的NIAMS研究人员跨学科小组更广泛的赠款申请提供初步数据。

DESCRIPTION (provided by applicant): Rheumatoid arthritis (RA) is a chronic, progressive, systemic, inflammatory disease that primarily attacks peripheral joints and surrounding tendons and ligaments. This often very painful and debilitating disease affects approximately 1.3 million Americans, of which about 70% are women. 10% of affected subjects suffer total disability. Over the last decade there have been considerable advances in the treatment of rheumatoid arthritis (RA). The use of biologic agents that antagonize tumor necrosis factor (TNF) has resulted in decreased morbidity as well as clinically meaningful improvement in quality of life. Nevertheless, a considerable proportion of RA patients, ranging from 20% to 50% in clinical trials, failed to mount a robust clinical response to these agents. Given the very high cost and potential serious toxicities associated with TNF antagonists, identification of predictors of the response to TNF antagonist therapy would help to optimize the clinical management of RA patients. Novel optical tomographic imaging (OTI) methods have been developed in recent years and are currently tested for various clinical application ranging from breast cancer imaging to imaging of brain activities. This novel technology promises to offer new insights into the various disease processes without the use of ionizing radiation at a relatively low cost. The group of Dr. Hielscher has recently shown that OTI is particularly sensitive to small changes in finger joints affected by RA. These changes manifest themselves in differences in the optical absorption and scattering coefficients inside these joints, which come about by changes in the optical properties of the synovial fluid as well as the vasculature surrounding the joints. We hypothesize that optical tomographic imaging (OTI) methods will be able to detect changes occurring in arthritic joints that are treated with TNF antagonist within the first few months or even weeks of treatment initiation. Therefore, the specific aim of this revision application is to perform a longitudinal observational pilot study with 20 RA patients to identify optical imaging biomarkers that can be used to predict treatment outcome. In particular we expect that patients who respond to the treatment will show an increase in the variation of the scattering and absorption coefficient across the joint. In addition, both absorption and scattering coefficients will decreas. In patients for whom treatment response is not observed, no changes will be observed over the course of the treatment. A successful study would provide preliminary data for a more extensive grant application by a newly formed interdisciplinary team of NIAMS researchers.