Improving the Management of Rheumatoid Arthritis-Associated Lung Disease in Veterans Using Real-World Data

使用真实世界数据改善退伍军人类风湿性关节炎相关肺部疾病的管理

• 批准号: 10426043
• 负责人: Bryant R England
• 金额: --
• 依托单位: OMAHA VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10426043
• 关键词: Acetaldehyde; Address; Adoption; Affect; Algorithms; Antibodies; Autoantibodies; Award; Big Data; Biological; Biological Markers; Biological Products; Biological Response Modifier Therapy; Cessation of life; Characteristics; Clinical; Clinical Investigator; Clinical Practice Guideline; Clinical Research; Data; Data Linkages; Data Sources; Disease; Disease Outcome; Disease Progression; Doctor of Philosophy; Effectiveness; Foundations; Future; General Population; Genes; Genetic Markers; Goals; Health Care Costs; Hospitalization; Immersion; Individual; Inflammatory; Interleukin-8; Interstitial Lung Diseases; Joints; Lead; Link; Lung Transplantation; Lung diseases; MUC5B gene; Malignant Neoplasms; Malondialdehyde; Matrilysin; Matrix Metalloproteinases; Medicare; Mentors; Mentorship; Methodology; Methods; Modeling; Observational Study; Outcome; Patients; Pharmacoepidemiology; Population; Positioning Attribute; Premature Mortality; Productivity; Prognosis; Prognostic Marker; Prospective cohort; Pulmonary Fibrosis; Pulmonary function tests; Quality of life; Reporting; Research; Research Personnel; Research Project Grants; Respiratory Disease; Rheumatoid Arthritis; Risk; Role; Safety; Selection for Treatments; Serum; Source; TNF gene; Time; Training Programs; Translational Research; Uncertainty; Veterans; Veterans Health Administration; Vital capacity; Work; active comparator; aggressive therapy; antifibrotic treatment; arthritis therapy; attributable mortality; career; chronic autoimmune disease; cohort; comparative effectiveness; comparative safety; compare effectiveness; cost; cytokine; design; disability; genetic variant; high risk; high risk population; idiopathic pulmonary fibrosis; immunomodulatory therapies; improved; indexing; inhibitor; innovation; meetings; mortality; mortality risk; multidisciplinary; novel; novel therapeutics; optimal treatments; overtreatment; personalized management; personalized medicine; physically handicapped; physiologic model; predictive modeling; prognostic; prognostic assays; programs; prospective; respiratory; rituximab; supplemental oxygen; tocilizumab; treatment strategy

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting 1.3 million individuals in the U.S., causing physical disability, reduced quality of life, premature mortality, and enormous health care costs. Veterans with RA die from respiratory diseases at a rate three times higher than the general population. Much of this excess respiratory mortality affecting Veterans with RA is attributable to interstitial lung disease (ILD), which has a prognosis as poor as many cancers. Despite advances in RA treatment over the past two decades with the adoption of novel therapies and more aggressive treatment strategies, the optimal management of RA-ILD is unknown. Two critical limitations for effectively managing Veterans with RA-ILD are 1) the inability to identify Veterans with progressive RA-ILD—those most likely to benefit from anti-fibrotic or aggressive immunomodulatory therapies and 2) a lack of data on the comparative effectiveness and safety of disease- modifying RA therapies in this population. Therefore, the overall objectives of this project are to leverage unique prospective Veteran RA-ILD cohorts and data linkages within the Veterans Health Administration (VHA) to 1) identify prognostic serum and genetic biomarkers for RA-ILD and 2) compare the effectiveness and safety of RA therapies in Veterans with RA-ILD. Our central hypotheses are that serum and genetic biomarkers will be independently associated with, and accurately predict, RA-ILD progression, and select RA therapies will differentially slow ILD progression and improve related survival. In Aim 1, we will utilize prospective RA-ILD cohorts to identify prognostic serum and genetic biomarkers and derive progressive RA-ILD predictive models. We hypothesize that biomarkers from RA-ILD pathophysiologic domains—novel disease-related autoantibodies, genetic markers, pro-inflammatory cytokines, and matrix metalloproteinases—will be independently associated with ILD progression in Veterans with RA-ILD. In Aim 2, we will link national VHA data sources and use advanced causal inference methodology to identify RA therapies that are associated with less ILD progression and improved survival in Veterans with RA-ILD. We hypothesize that compared to tumor necrosis factor inhibitors (TNFi), non-TNFi biologic therapies (rituximab, abatacept, and tocilizumab) will be associated with less ILD progression and have a lower mortality risk in Veterans with RA-ILD. Impact: The results from the proposed research will assist clinicians with personalized treatment selection in Veterans with RA-ILD, a high-risk population with little data to currently guide treatment selection. The PI will complete this research plan under the mentorship of a multidisciplinary team of experts in clinical and pharmacoepidemiologic research within the VHA, building upon his early research productivity. The accompanying mentored training program in pharmacoepidemiology and causal inference methodology obtained through advanced, immersive coursework and professional meetings will position the PI to conduct high-impact research in RA and RA-ILD within the VHA. Upon completion of this award, the PI will be poised for an independent research career targeting improvements in the long-term outcomes for Veterans with RA.

类风湿关节炎（RA）是一种慢性自身免疫性疾病，影响了美国130万人，导致 身体残疾，生活质量降低，过早死亡和巨大的医疗保健费用。退伍军人 RA因呼吸道疾病而死亡，比一般人群高三倍。大部分超过 影响RA的退伍军人的呼吸道死亡率归因于间质性肺疾病（ILD），该疾病具有 预后和许多癌症一样差。尽管在过去的二十年中，RA治疗方面取得了进步 采用新型疗法和更具侵略性的治疗策略，RA-ELD的最佳管理是 未知。有效管理具有RA-ild的退伍军人的两个关键局限性是1）无法识别 具有渐进式RA-ild的退伍军人 - 最有可能受益于抗纤维化或侵略性 免疫调节疗法和2）缺乏有关疾病的比较有效性和安全性的数据 修改该人群中的RA疗法。因此，该项目的总体目标是利用 退伍军人卫生管理局（VHA）内的独特的潜在资深RA-ILD同伙和数据联系 到1）确定RA-ILD的预后血清和遗传生物标志物和2）比较有效性和安全性 与RA-ELD的退伍军人的RA疗法。我们的中心假设是血清和遗传生物标志物将 独立地与RA-ILD进展并准确预测，选择RA疗法将会 差异降低了ILD进展并改善了相关的生存率。在AIM 1中，我们将利用潜在的RA-ELD 鉴定预后血清和遗传生物标志物并得出进行性RA-ILD预测模型的人群。 我们假设来自RA-ILD病理生理领域的生物标志物 - 与疾病相关的生物标志物 自身抗体，遗传标记，促炎细胞因子和基质金属蛋白酶 - 将是 在AIM 2中，我们将链接国家VHA 数据源并使用先进的因果推理方法来识别相关的RA疗法 ILD的进展较少，在具有RA-dild的退伍军人中的生存率提高。我们假设这与 肿瘤坏死因子抑制剂（TNFI），非TNFI生物疗法（利妥昔单抗，Abatacept和Tocilizumab）将 与RA-ELD的退伍军人相关的ILD进展较少，死亡率较低。影响： 拟议研究的结果将帮助临床医生在退伍军人中进行个性化治疗选择 RA-sild是一个高风险人群，目前很少有数据指导治疗选择。 PI将完成此操作 在临床专家组成的多学科团队的心态下的研究计划 VHA内部的药物ePIDEMIologic研究基于他早期的研究生产力。这 参加药物epidemiology和Causal推论方法的培训计划 通过高级，沉浸式课程和专业会议获得的将使PI定位 VHA内的RA和RA-ELD的高影响力研究。完成此奖项后，PI将被中毒 为了独立研究职业，针对RA的退伍军人长期成果的改善。