Background Ivacaftor (IVA) has been shown to improve lung function and other clinical outcomes in people with cystic fibrosis (CF). A decade of real-world IVA availability has enabled the examination of long-term outcomes with this treatment. This retrospective, longitudinal cohort study investigated the impact of IVA on mortality rate and health outcomes among people with CF in the US. Methods Data from the US CF Foundation Patient Registry from January 2010 to December 2019 were analysed. The IVA-treated cohort included people with a CF transmembrane conductance regulator ( CFTR ) gating mutation (excluding R117H ); age-matched comparator cohort included people with a F508del and a minimal function CFTR mutation who had no prior CFTR modulator treatment. Baseline characteristics were balanced between cohorts using standardised mortality ratio weighting generated from propensity scores. Outcomes of interest were overall survival, lung transplant, percent predicted forced expiratory volume in 1 s (ppFEV1), body mass index (BMI), pulmonary exacerbations (PEx), outpatient visits and hospitalisations. Findings Over a maximum follow-up of 7.9 years, the IVA-treated cohort (N=736) had lower rates of mortality (hazard ratio \[HR\] (95% CI): 0.22 (0.09 to 0.45)), lung transplant (HR: 0.11 (95% CI 0.02 to 0.28)), PEx (rate ratio: 0.49 (95% CI 0.42 to 0.55)) and all-cause hospitalisations (rate ratio: 0.50 (95% CI 0.43 to 0.56)) as well as better lung function (mean difference in ppFEV1: 8.46 (95% CI 7.34 to 9.75)) and higher BMI/BMI z -scores (mean difference 1.20 (95% CI 0.92 to 1.71) kg/m2 and 0.27 (95% CI 0.25 to 0.40), respectively) than the comparator cohort (N=733). Interpretation Our analysis suggests that IVA provides sustained clinical benefits in people with CF over a follow-up period of approximately 8 years. These findings reinforce the existing real-world evidence that IVA can slow disease progression and decrease the healthcare burden of CF over the long term. Data are available on reasonable request. The data supporting the findings of this study are available from the US CFFPR at . The US CFFPR collects and manages its own data and maintains processes for researchers to request summarised data. Restrictions may apply to the availability of these data, which were used under the licence agreement for this study.

中文翻译：

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依伐卡托对囊性纤维化患者死亡率和健康结局的长期影响


背景 依伐卡托 （IVA） 已被证明可以改善囊性纤维化 （CF） 患者的肺功能和其他临床结局。十年来真实世界 IVA 的可用性使这种治疗的长期结果的检查成为可能。这项回顾性纵向队列研究调查了 IVA 对美国 CF 患者死亡率和健康结局的影响。方法 分析了 2010 年 1 月至 2019 年 12 月来自美国 CF 基金会患者登记处的数据。IVA 治疗的队列包括患有 CF 跨膜电导调节因子 （CFTR） 门控突变 （不包括 R117H） 的人;年龄匹配的对照组包括具有 F508del 和最小功能 CFTR 突变且既往未接受过 CFTR 调节剂治疗的人。使用倾向评分生成的标准化死亡率比加权在队列之间平衡基线特征。感兴趣的结局是总生存期、肺移植、1 秒预测用力呼气容积百分比 （ppFEV1）、体重指数 （BMI）、肺部恶化 （PEx）、门诊就诊和住院。结果在最长 7.9 年的随访中，IVA 治疗队列 （N=736） 的死亡率较低 （风险比 \[HR\] （95% CI）：0.22 （0.09 至 0.45））、肺移植 （HR： 0.11 （95% CI 0.02 至 0.28））、PEx （比率比： 0.49 （95% CI 0.42 至 0.55））和全因住院 （比率比： 0.50 （95% CI 0.43 - 0.56）））以及更好的肺功能（ppFEV1 的平均差异： 8.46 （95% CI 7.34 至 9.75）） 和 BMI/BMI z 评分 （平均差分别为 1.20 （95% CI 0.92 至 1.71） kg/m2 和 0.27 （95% CI 0.25 至 0.40） ）高于对照组队列 （N=733）。 解释我们的分析表明，IVA 在大约 8 年的随访期内为 CF 患者提供了持续的临床益处。这些发现强化了现有的真实世界证据，即 IVA 可以减缓疾病进展并长期减轻 CF 的医疗保健负担。数据可应合理要求提供。支持这项研究结果的数据可从美国 CFFPR 获得，网址为 。美国 CFFPR 收集和管理自己的数据，并维护研究人员请求汇总数据的流程。这些数据的可用性可能受到限制，这些数据是根据本研究的许可协议使用的。