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: 10543981
• 负责人: Alexandra Toporek
• 金额: $ 7.64万
• 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/10543981
• 关键词: Accreditation; Acute; Address; Adherence; Adult; Affect; Alleles; Antibiotic Therapy; Antibiotics; Azithromycin; Bronchiectasis; Caring; Caucasians; Chlorides; Chronic; Clinical; Clinical Data; Consumption; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Data; Delta F508 mutation; Diagnosis; Foundations; Frequencies; Functional disorder; Future; Genetic Diseases; Goals; Guidelines; Hereditary Disease; Home; Hospitalization; Hospitals; Hour; Hydration status; Individual; Inhalation; Intravenous; Lung; Lung diseases; Macrolides; Maintenance Therapy; Modification; Morbidity - disease rate; Mucociliary Clearance; Mucous body substance; Mutation; Nebulizer; Observational Study; Obstructive Lung Diseases; Oral; Outcome; Patients; Pattern; Persons; Pharmaceutical Preparations; Population; Practice Management; Proteins; Provider; Pulmonary Function Test/Forced Expiratory Volume 1; Regimen; Regulator Genes; Reporting; Research; Route; Saline; Surveys; Symptoms; Time; United States; Update; VX-770; Weight; airway surface liquid; body system; chronic infection; clinical care; cohort; cystic fibrosis patients; design; experience; improved; lung health; mortality; phase III trial; prospective; pulmonary function; pulmonary function decline; targeted treatment

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电导调节剂突变引起的 （CFTR）蛋白质，导致气道粘液，慢性感染和支气管扩张。每天很多 CF基金会（CFF）建议疗法治疗这些并发症，包括吸入 高渗盐水，多氨酸酶Alfa和抗生素，口服阿奇霉素和气道清除疗法。从历史上看 遵守这些疗法非常低，因为它们非常耗时，最多需要2-4个小时才能 每天完成。 CF患者的症状也急性恶化，称为肺部恶化 （PEX），用全身性抗生素治疗，与进行性肺功能下降和 死亡率增加。 CFTR调节器旨在逆转CFTR功能障碍。在CFTR的批准下 调节剂Elexacaftor/tezacaftor/ivacaftor（ETI），90％的CF人群有资格获得高效 调节剂治疗（HEMT），定义为CFTR调节剂治疗，导致百分比大幅增加 预测FEV1和汗水氯化物浓度的改善。在批准ETI之前，只有约5％ 患者有资格接受HEMT治疗。我们的本地数据表明，ETI的大多数患者报告说 在与CF提供者讨论后，他们简化了慢性治疗方案 与这些疗法相关的负担以及他们开始ETI后经历的症状的改善。 同样，我们的CF中心报告的提供者报告在家庭环境中开处方口服抗生素以治疗 ETI患者更频繁地医院中的PEX而不是静脉内（IV）抗生素。细节 国家实践模式如何在长期维护疗法和管理方面发生变化 PEX的批准仍然不确定。我们假设提供者修改了 对CF的慢性和急性疗法的治疗，使得CF的方法不那么侵略性， 需要更少的慢性药物和PEX的繁重治疗方法。 当前的研究将：（1）利用全国调查来评估CF提供者实践模式，评估 如果提供者继续遵循ETI患者的慢性和急性疗法指南。如果修改 制作了，我们将评估修改了哪些慢性疗法，并且口服和IV的频率变化 ETI患者的PEX治疗的抗生素使用和住院治疗； （2）评估管理 前瞻性的PEX在我们中心确定口服的比例与IV抗生素和治疗的比例是 自ETI批准以来，家庭与医院环境发生了变化。该提案的结果解决了 关于在HEMT时代不断发展的CF管理的重要问题，并具有直接影响 CF患者的临床护理。如果我们的结果表明自从提供者实践发生了变化 批准ETI，需要进一步的研究以确定这些变化是否与恶化相关 临床结果和更新应相应地符合临床护理指南。