Risk and impact of infection resulting from treatment with chronic glucocorticoids in patients with rheumatoid arthritis

项目摘要 风湿性关节炎（RA）是一种常见的自身免疫性疾病，影响1%的人口， 发病率和死亡率都很高治疗进展改善了疾病控制，但感染 仍然是免疫抑制治疗的主要并发症。糖皮质激素被用作长期治疗 在30-60%的RA患者中，可能是RA感染风险的主要因素。众所周知的是 较高剂量的糖皮质激素具有非常高的感染风险，但更常用的低剂量治疗的风险 仍然未知。确定低剂量糖皮质激素的感染风险已被确定为一个关键领域， 研究，需要告知治疗策略，以改善RA患者的结局。 本研究的目的是确定低剂量糖皮质激素是否与 1）需要住院治疗的严重感染或2）不会导致 住院我们将通过应用先进的 两个大型索赔数据库和一个纵向登记研究，包括 疾病活动的测量。通过进行倾向调整分析和一个新的工具变量， 基于糖皮质激素处方的变异性分析，我们将提供最全面的 迄今为止使用糖皮质激素的感染风险评估。需要一种不同的方法来研究非- 住院感染。这些感染比住院感染常见20倍以上， 在现有数据源中无法准确识别。我们将进行一项前瞻性研究， 评估来衡量这些感染，从一个大型的在线患者登记处招募患者。额外 这项工作的主要目标是确定常见感染对患者的影响。 博士乔治的职业目标是成为一名研究治疗安全性和有效性的独立调查员 改善风湿病患者的预后。他和他的导师们创造了一个全面的 职业发展计划，利用他的导师团队的独特技能和资源 在Penn。在导师团队的指导下，通过正式的课程和实践经验， 利用他目前在流行病学方面的培训和使用行政索赔数据的经验。他将获得技能 在先进的药物流行病学，包括工具变量分析，他将开发新的 前瞻性患者导向研究的专业知识，这是开发未来干预研究所需的关键技能 以补充观测数据。通过这项工作，在他的导师团队的指导下，他将 获得所需的技能和经验，推出一个成功的职业生涯作为一个独立的医生科学家， 成为类风湿关节炎研究的领导者。

PROJECT SUMMARY Rheumatoid arthritis (RA) is a common autoimmune condition affecting 1% of the population and is associated with substantial morbidity and mortality. Treatment advances have improved disease control, but infections remain a major complication of immunosuppressive treatment. Glucocorticoids are used as long-term therapy in 30-60% of patients with RA and are potentially a major contributor to infection risk in RA. It is well known that higher glucocorticoid doses carry very high infection risk, but risk with more commonly used low-dose therapy remains unknown. Defining infection risk with low-dose glucocorticoids has been identified as a critical area for research, needed to inform treatment strategies to improve outcomes in patients with RA. The objective of this study is to determine whether low-dose glucocorticoids are associated with an increase in the risk of 1) serious infections requiring hospitalization or 2) common infections that do not lead to hospitalization. We will examine the risk of serious infections requiring hospitalization by applying advanced pharmacoepidemiologic methods to two large claims databases and a longitudinal registry that includes disease activity measures. By conducting a propensity-adjusted analysis and a novel instrumental variable analysis based on the variability in the prescribing of glucocorticoids, we will provide the most comprehensive evaluation of infection risk with glucocorticoids to date. A different approach is needed to study non- hospitalized infections. These infections are more than 20 times more common than hospitalized infections but cannot be accurately identified in existing data sources. We will conduct a prospective study with frequent assessments to measure these infections, recruiting patients from a large online patient registry. An additional key goal of this work will be to determine the impact of common infections on patients. Dr. George's career goal is to become an independent investigator studying treatment safety and effectiveness to improve outcomes in patients with rheumatic disease. He and his mentors have created a comprehensive career development plan that takes advantage of the unique skills of his mentorship team and the resources available at Penn. With formal coursework and hands-on experience guided by his mentorship team, he will build on his current training in epidemiology and experience using administrative claims data. He will gain skills in advanced pharmacoepidemiology including instrumental variable analysis, and he will develop new expertise in prospective patient-oriented research, a critical skill needed to develop future interventional studies to complement observational data. Through this work, and with the guidance of his mentorship team, he will gain the skills and experience needed to launch a successful career as an independent physician scientist and become a leader in rheumatoid arthritis research.