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

项目总结 类风湿关节炎(RA)是一种常见的自身免疫性疾病，影响1%的人口，并与 有相当高的发病率和死亡率。治疗的进步改善了疾病的控制，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%的类风湿关节炎患者中，并可能是类风湿关节炎感染风险的主要贡献者。众所周知， 较高剂量的糖皮质激素具有非常高的感染风险，但使用更常用的低剂量治疗则有风险。 仍然不为人知。确定使用小剂量糖皮质激素的感染风险已被确定为 研究，需要提供治疗策略，以改善类风湿关节炎患者的结果。 这项研究的目的是确定小剂量糖皮质激素是否与 1)需要住院的严重感染的风险或2)不会导致 住院治疗。我们将研究需要住院的严重感染的风险，通过应用先进的 两个大型索赔数据库和一个纵向登记的药物流行病学方法，包括 疾病活跃性衡量标准。通过进行倾向调整的分析和一个新的工具变量 根据对糖皮质激素处方的可变性分析，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，但 无法在现有数据源中准确标识。我们将经常进行前瞻性研究 评估以衡量这些感染，从大型在线患者登记中招募患者。一项额外的 这项工作的主要目标将是确定常见感染对患者的影响。 乔治博士的职业目标是成为一名研究治疗安全性和有效性的独立研究员 以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，利用他的指导团队的独特技能和资源 在宾夕法尼亚大学有售。在他的指导团队的指导下，有了正式的课程和实践经验，他将 以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为基础。他将获得技能 在包括工具变量分析在内的高级药物流行病学方面，他将开发新的 以患者为中心的前瞻性研究方面的专业知识，这是发展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，并在他的指导团队的指导下，他将 获得所需的技能和经验，作为一名独立的内科科学家和 成为类风湿性关节炎研究的领先者。

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.