WS01.04Elexacaftor/tezacaftor/ivacaftor reduces the risk of lung transplantation or death among people with advanced CF lung disease in the United States

IF 5.4 2区医学 Q1 RESPIRATORY SYSTEM

Journal of Cystic Fibrosis Pub Date : 2025-06-01 DOI:10.1016/j.jcf.2025.03.495

E. Cromwell , J. Todd , R.H. Keogh , C. Lesko , A.W. Brown , E. Tallarico , K.J. Ramos , A. Faro

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引用次数: 0

Abstract

Objectives

Individuals with advanced CF lung disease (ACFLD) are at increased risk of clinical deterioration, including death or lung transplant. This population was excluded from clinical trials but represent a group that could experience clinical benefit. We hypothesized that elexacaftor/tezacaftor/ivacaftor (ETI) would reduce the risk of death or first lung transplant among people with ACFLD.

Methods

We used the CF Foundation Patient Registry to identify individuals with ACFLD defined as those with lung function consistently below ppFEV₁ <40, report of massive hemoptysis or pneumothorax, supplemental oxygen use or referral for transplantation. We emulated a target trial using sequential trials to include anyone with ACFLD prescribed ETI between July 2019 and December 2023 and those never prescribed ETI in that period, including those ineligible. Weighted Cox proportional hazards models for competing risks were used to estimate the effect of ETI on time to pre-transplant death and first lung transplant. Risk differences for death 4 years post-ETI were also estimated.

Results

Among 4,221 individuals, 3,302 (78.2%) were prescribed ETI at some point between July 2019-December 2023. There were 138 deaths and 51 transplants among those prescribed ETI and 168 deaths and 117 transplants among those never prescribed. ETI prescription had hazard ratios of 0.38 (95% CI: 0.27; 0.51) for death and 0.27 (95% CI: 0.18; 0.42) for lung transplantation. The risk difference for death was 5.6% lower with ETI use (95% CI: 4.0; 7.3) after 4 years.

Conclusions

ETI reduced the risk of death or first transplant among people with ACFLD, critical outcomes in a high-risk population not included in the original clinical trials. These findings can be used by providers and patients to understand the impact of ETI on disease trajectory in ACFLD. Additionally, these findings help quantify the potential impact of ETI in settings where it is not yet available.

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在美国，elexacaftor /tezacaftor/ivacaftor可降低晚期CF肺病患者肺移植或死亡的风险

晚期CF肺病（ACFLD）患者临床恶化的风险增加，包括死亡或肺移植。该人群被排除在临床试验之外，但代表了一个可以体验临床获益的群体。我们假设elexaftor /tezacaftor/ivacaftor （ETI）可以降低ACFLD患者死亡或首次肺移植的风险。方法：我们使用CF基金会患者登记处来识别ACFLD患者，ACFLD定义为肺功能始终低于ppFEV1 <；40，报告大量咯血或气胸，补充氧气或转诊移植。我们使用顺序试验模拟了一项目标试验，包括在2019年7月至2023年12月期间患有ACFLD的患者和在此期间从未服用过ETI的患者，包括那些不符合条件的患者。采用竞争风险加权Cox比例风险模型来估计ETI对移植前死亡时间和首次肺移植的影响。eti后4年的死亡风险差异也进行了估计。结果在4221名患者中，有3302人（78.2%）在2019年7月至2023年12月的某个时间点接受了ETI治疗。在开药的患者中，有138人死亡和51例移植，而在没有开药的患者中，有168人死亡和117例移植。ETI处方的风险比为0.38 (95% CI: 0.27；0.51)和0.27 (95% CI: 0.18；0.42)。使用ETI后，死亡风险差异降低5.6% (95% CI: 4.0；7.3) 4年后。结论：seti降低了ACFLD患者的死亡或首次移植风险，这是最初临床试验中未包括的高危人群的关键结局。这些发现可以被提供者和患者用来了解ETI对ACFLD疾病轨迹的影响。此外，这些发现有助于量化ETI在尚未可用的环境中的潜在影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cystic Fibrosis 医学-呼吸系统

CiteScore

10.10

自引率

13.50%

发文量

1361

审稿时长

50 days

期刊介绍： The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.