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

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，导致呼吸道粘液增厚、慢性感染和支气管扩张。每天有很多人 CF基金会(CFF)建议使用包括吸入性治疗在内的治疗方法来治疗这些并发症 高渗盐水、α-半乳糖胺、抗生素、口服阿奇霉素和呼吸道清除疗法。从历史上看， 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个小时 每天都要完成。患有CF的人也有急性症状恶化，称为肺恶化 (Pex)，用全身抗生素治疗，并与进行性肺功能下降和 死亡率上升。Cftr调节剂旨在逆转cftr功能障碍。在CFTR的批准下 调制器电工/电工/电工(ETI)，90%的CF人口有资格获得高效 调节器疗法(HEMT)，定义为CFTR调节器疗法，可显著提高 预测FEV1和汗氯化物浓度的改善。在ETI批准之前，只有~5%的 患者有资格接受HEMT治疗。我们的本地数据显示，ETI上的大多数患者报告说 他们在与CF供应商讨论后简化了他们的慢性治疗方案，考虑到 与这些治疗相关的负担以及他们开始ETI后所经历的症状的改善。 同样，我们CF中心的提供者报告说，在家庭环境中开出口服抗生素治疗 对于接受ETI的患者，在医院更频繁地使用PEX而不是静脉(IV)抗生素。详细内容如下： 在慢性维持疗法和管理方面，国家实践模式发生了怎样的变化 自ETI批准以来，Pex的地位仍不确定。我们假设提供商已经修改了 慢性和急性治疗慢性充血性心力衰竭的管理，使治疗充血性心力衰竭的方法不那么激进， 对于Pex来说，需要更少的慢性药物和更少的负担治疗。 目前的研究将：(1)利用全国调查来评估CF提供商的实践模式，评估 如果供应商继续遵循ETI患者的慢性和急性治疗指南。如果修改 ，我们将评估哪些慢性疗法被修改，以及口服和静脉注射频率的变化 ETI患者Pex的抗生素使用和住院管理；(2)评价管理 在我们的中心前瞻性地确定口服和静脉注射抗生素的比例和治疗在 自ETI批准以来，家庭与医院的设置发生了变化。这项提案的结果解决了一个 HEMT时代关于现金流转管理演变的重要问题及其直接意义 用于CF患者的临床护理。如果我们的结果表明提供商的做法自 ETI的批准，需要进一步的研究来确定这些变化是否与病情恶化有关 临床结果和临床护理指南应相应更新。

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.