Changes in Provider Practices for the Management of Cystic Fibrosis (CF) in the Era of Highly Effective Modulator Therapy

高效调节剂治疗时代囊性纤维化 (CF) 治疗提供者实践的变化

• 批准号: 10312402
• 负责人: Alexandra Toporek
• 金额: $ 8.9万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-23 至 2023-09-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10312402
• 关键词: Changes; Provider; Practices; Management; Cystic

Cystic Fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which result in thickened airway mucus, chronic infection, and bronchiectasis. Many daily therapies are recommended by the CF Foundation (CFF) to treat these complications, including inhaled hypertonic saline, dornase alfa, and antibiotics, oral azithromycin, and airway clearance therapies. Historically, adherence to these therapies is quite low, as they are exceedingly time consuming, requiring up to 2-4 hours to complete daily. Persons with CF also have acute worsening of symptoms, called pulmonary exacerbations (PEx), that are treated with systemic antibiotics and are associated with progressive lung function decline and increased mortality. CFTR modulators aim to reverse CFTR dysfunction. With the approval of the CFTR modulator elexacaftor/tezacaftor/ivacaftor (ETI), 90% of the CF population is eligible for highly effective modulator therapy (HEMT), defined as CFTR modulator therapy resulting in a substantial increase in percent predicted FEV1 and improvement in sweat chloride concentrations. Prior to the approval of ETI, only ~5% of patients were eligible for therapy with HEMT. Our local data show that a majority of patients on ETI report that they have simplified their chronic therapy regimens following discussion with their CF providers, given the burden associated with these therapies and improvement in symptoms they experienced after starting ETI. Likewise, providers at our CF center report prescribing oral antibiotics in the home setting for the treatment of PEx rather than intravenous (IV) antibiotics in the hospital more frequently for patients on ETI. The details of how national practice patterns have changed with regards to chronic maintenance therapies and management of PEx since the approval of ETI remains uncertain. We hypothesize that providers have modified the management of both chronic and acute therapies for CF such that the approach to CF is less aggressive, requiring fewer chronic medications and less burdensome treatments for PEx. This current study will: (1) utilize a national survey to evaluate CF provider practice patterns, assessing if providers continue to follow guidelines for chronic and acute therapies in patients on ETI. If modifications were made, we will assess what chronic therapies were modified and changes in the frequency of oral and IV antibiotic use and hospitalizations for the management of PEx in patients on ETI; (2) evaluate the management of PEx prospectively at our center to determine if the proportion of oral vs. IV antibiotics and treatment in the home vs. hospital setting has changed since the approval of ETI. The results of this proposal address an important question regarding the evolving management of CF in the era of HEMT and have direct implications for the clinical care of persons with CF. If our results suggest that provider practices have changed since the approval of ETI, further research is necessary to determine if these changes are associated with worsened clinical outcomes and updates should be made to clinical care guidelines accordingly.

囊性纤维化（CF）是由囊性纤维化跨膜传导调节因子突变引起的 CFTR蛋白，其导致气道粘液增厚、慢性感染和支气管扩张。许多日常 CF基金会（CFF）推荐治疗这些并发症，包括吸入 高渗盐水、阿法链道酶和抗生素、口服阿奇霉素和气道清除疗法。从历史上看， 对这些疗法的依从性相当低，因为它们非常耗时，需要长达2-4小时来 每天完成。患有CF的人也会出现症状急性恶化，称为肺加重 (PEx)，接受全身性抗生素治疗并与进行性肺功能下降相关， 增加死亡率。CFTR调节剂旨在逆转CFTR功能障碍。经CFTR批准， 调节剂elexacaftor/tezacaftor/ivacaftor（ETI），90%的CF人群有资格获得高效 调制器治疗（HEMT），定义为CFTR调制器治疗，导致百分比大幅增加 预测FEV 1和汗液氯化物浓度的改善。在ETI批准之前，只有约5%的 患者适合接受HEMT治疗。我们的本地数据显示，大多数接受ETI治疗的患者报告称， 他们在与CF提供者讨论后简化了慢性治疗方案， 与这些治疗相关的负担和开始ETI后经历的症状改善。 同样，我们CF中心的提供者报告说，在家庭环境中开口服抗生素治疗 对于ETI患者，在医院更常使用PEX而不是静脉注射（IV）抗生素。的细节 慢性维持疗法和管理方面的国家实践模式如何发生变化 自ETI批准以来，PEX的价格仍不确定。我们假设供应商已经修改了 管理CF的慢性和急性治疗，使得CF的方法不那么具有侵略性， 需要更少的慢性药物和更少的PEx治疗负担。 目前的研究将：（1）利用全国调查，以评估CF供应商的做法模式，评估 如果提供者继续遵循对ETI患者的慢性和急性治疗指南。修改是否 我们将评估哪些慢性治疗被修改，以及口服和静脉注射频率的变化。 抗生素使用和治疗ETI患者PEX的住院情况;（2）评价治疗 的PEx，以确定口服与静脉注射抗生素的比例和治疗中， 自ETI批准以来，家庭与医院环境发生了变化。该提案的结果涉及一个 重要的问题，关于不断发展的管理CF在HEMT的时代，并有直接的影响 用于CF患者的临床护理。如果我们的结果表明，自2010年以来， 批准ETI后，有必要进行进一步的研究，以确定这些变化是否与 临床结果和临床护理指南应相应更新。