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Use and Effectiveness of Infection Prophylaxis Strategies in a National Cohort of Patients with ANCA Vasculitis

感染预防策略在全国 ANCA 血管炎患者队列中的使用和有效性

基本信息

批准号：
10350714
负责人：
Carolyn Timberlake Thorpe
金额：
$ 15.55万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-02-13 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10350714
关键词：
ANCA vasculitis Address Amoxicillin Anti-Bacterial Agents Anti-Inflammatory Agents Antibiotics Antifungal Agents Autoimmune Diseases Blood Blood Vessels Chronic Clinical Data Decision Making Development Disease Doxycycline Drug Prescriptions Effectiveness Entropy Equilibrium Event Face Fee-for-Service Plans Fluoroquinolones Foundations Future Goals Guidelines Healthcare Immunosuppression Infection Infection prevention Inflammation Kidney Life Medical Medicare Medicare claim Methods Morbidity - disease rate Necrosis Observational Study Opportunistic Infections Organ Outcome Patients Pharmaceutical Preparations Pharmacoepidemiology Pneumocystis carinii Pneumonia Population Population Study Predictive Factor Prevention Property Prophylactic treatment Provider Randomized Controlled Trials Rare Diseases Regression Analysis Relapse Reporting Research Research Design Respiratory Tract Infections Retrospective cohort study Risk Selection Bias Skin Therapeutic immunosuppression Time Treatment Effectiveness Trimethoprim-Sulfamethoxazole Urinary tract Use Effectiveness Variant Weight active comparator antimicrobial beneficiary cohort comparative effectiveness trial design effectiveness evaluation evidence base immunosuppressed improved infection burden infection risk mortality mortality risk multidisciplinary patient population population based prevent prophylactic prospective test randomized trial standard of care therapy development treatment comparison treatment guidelines trial comparing

项目摘要

PROJECT SUMMARY/ABSTRACT Reducing infection risk is a priority in patients with antineutrophil cytoplasmic autoantibody (ANCA) – associated vasculitis (AAV), a group of rare, life-threatening autoimmune diseases that cause inflammation and necrosis of blood vessels in multiple organs, most commonly the kidneys. The availability of effective, aggressive immunosuppressive medications transformed AAV from a rapidly fatal condition to a chronic, relapsing-remitting disease, but comes with a high burden of severe infections, which are now the leading cause of morbidity and mortality in AAV. To prevent opportunistic infection with Pneumocystis jirovecii pneumonia (PJP), treatment guidelines recommend prophylaxis with trimethoprim/sulfamethoxazole (TMP/SMX). However, PJP occurs very rarely in AAV, even in those not receiving prophylaxis. Other severe infections are common and may be effectively prevented by alternative prophylactic antimicrobials (e.g., fluoroquinolones, doxycycline, amoxicillin, antifungals) recommended for non-AAV immunosuppressed populations. Limited available data suggests under-utilization and widespread variation in use of recommended and alternative prophylaxis strategies, but generalizable information about drivers of this variation is lacking. In addition, we lack evidence from randomized trials or rigorous observational studies designed to assess causal effects of recommended and alternative prophylaxis on key outcomes in AAV, including severe infections and mortality. The long-term goal of this research is to reduce infection-related morbidity and mortality in AAV, through improved understanding of the determinants of patients’ use of prophylaxis and evidence regarding effectiveness of recommended vs. alternative prophylaxis. The proposed retrospective cohort study will use medical claims and prescription drug data for a national cohort of Medicare beneficiaries with AAV who initiate a new course of immunosuppressive therapy in 2016-2017. Specific aims are to (1) identify predisposing, enabling, and medical need (i.e., clinical) factors associated with use of TMP/SMX prophylaxis, alternative prophylaxis strategies, or no prophylaxis; and (2) assess the effectiveness of antimicrobial prophylaxis strategies in reducing risk of severe infections and mortality. Aim 1 analyses will use regression analyses to identify factors associated with use of guideline-recommended TMP/SMX prophylaxis or alternative prophylaxis strategies, versus no prophylaxis. Aim 2 will use powerful pharmacoepidemiologic methods to reduce potential for selection bias and confounding, including an active-comparator, new-user design and advanced covariate balancing methods (i.e., entropy balancing), to compare severe infection and mortality risk in those receiving TMP/SMX vs. alternative prophylaxis. This study will identify patients most at-risk for not receiving recommended prophylaxis, improve the evidence base to inform decision-making about prophylaxis in AAV, and build a foundation for future comparative effectiveness trials comparing promising alternative prophylaxis strategies to the current standard of care in this understudied population.

项目摘要/摘要降低感染风险是抗中性粒细胞胞浆抗体(ANCA)患者的首要任务。相关性血管炎(AAV)是一组罕见的、危及生命的自身免疫性疾病，可引起炎症以及多个器官的血管坏死，最常见的是肾脏。可获得有效的、积极的免疫抑制药物将AAV从迅速致命的状态转变为慢性、复发-缓解性疾病，但伴随着严重感染的高负担，这现在是主要的 AAV发病和死亡的原因。预防日本肺孢子虫机会性感染肺炎(PJP)，治疗指南建议使用甲氧苄啶/磺胺甲恶唑预防 (TMP/SMX)。然而，PJP在AAV中很少发生，即使在那些没有接受预防的患者中也是如此。其他严重的感染是常见的并且可以通过替代的预防性抗菌剂(例如，氟喹诺酮类、多西环素、阿莫西林、抗真菌药)推荐用于非AAV免疫抑制人口。有限的可用数据表明，建议的使用未得到充分利用和广泛变化和替代的预防策略，但缺乏关于这种变异的驱动因素的概括性信息。在……里面此外，我们缺乏来自随机试验或旨在评估因果关系的严格观察性研究的证据。推荐和替代预防措施对AAV关键结局的影响，包括严重感染和死亡率。这项研究的长期目标是降低AAV感染相关的发病率和死亡率，通过更好地理解患者使用预防措施的决定因素和证据推荐预防措施与替代预防措施的有效性。拟议的回溯性队列研究将使用发起AAV的国家医疗保险受益人队列的医疗索赔和处方药数据 2016-2017年新的免疫抑制治疗疗程。具体目标是(1)识别诱因，与使用TMP/SMX预防替代方案相关的使能和医疗需要(即临床)因素预防策略，或不预防；以及(2)评估抗菌素预防的有效性减少严重感染和死亡风险的战略。目标1分析将使用回归分析来确定与使用指南推荐的TMP/SMX预防措施或替代方案相关的因素预防策略，而不是不预防。Aim 2将使用强大的药物流行病学方法减少选择偏差和混淆的可能性，包括有源比较器、新用户设计和高级协变量平衡方法(即，熵平衡)，用于比较严重感染和死亡风险在接受TMP/SMX与替代预防的患者中。这项研究将确定NOT的最高风险患者接受建议的预防措施，改善证据基础，为预防措施的决策提供信息在AAV中，并为未来比较有希望的替代方案的比较有效性试验奠定基础在这一研究不足的人群中，针对目前的护理标准制定预防策略。