The cystic fibrosis transmembrane conductance regulator (CFTR) modulator compound, ivacaftor, reached its 10-year anniversary of US Food and Drug Administration (FDA) approval in 2022. This long-standing experience captured within US CF foundation patient registry (US CFFPR) data up to December 2019 was harnessed by Merlo and colleagues in this edition of the journal to provide further insight into its ability to improve health outcomes. In the first study,1 the authors used US CFFPR data between 2010 and 2019 to examine health effects observed over a mean follow-up period of approximately 6 years (maximum 7.9 years), the longest follow-up to date in the literature. An ivacaftor-treated cohort of 736 people with cystic fibrosis (pwCF) with a gating mutation (excluding R117H) were compared with an age-matched comparator cohort with F508del and a minimal function CFTR variant who were CFTR modulator naïve. A greater than eight point difference in FEV1 percent predicted (ppFEV1) was observed between the cohorts, with the magnitude of difference increasing over time both within the overall cohort, and in each of the different age groups examined (6–11, 12–17 and ≥18 years). The greatest magnitude of change over time occurred among 12–17 year olds. Accompanying benefits were observed in body mass index, rates of pulmonary exacerbation (PEx) and all-cause hospitalisation. Rate of lung transplant and mortality rate were also lower in the ivacaftor-treated cohort. When interpreting these results, two aspects are important to interrogate. First, the validity of the comparison group. The molecular consequence of minimal function variants are felt to be similar to that of F508del,2 and US CFFPR-based …

中文翻译：

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衰老和 ivacaftor：揭示长期影响


囊性纤维化跨膜电导调节剂 (CFTR) 调节剂化合物 ivacaftor 于 2022 年迎来美国食品和药物管理局 (FDA) 批准 10 周年。这一长期经验记录在美国 CF 基金会患者登记 (US CFFPR) 数据中Merlo 及其同事在本期杂志中利用截至 2019 年 12 月的数据，进一步深入了解其改善健康结果的能力。在第一项研究1中，作者使用 2010 年至 2019 年的美国 CFFPR 数据来检查在平均约 6 年（最长 7.9 年）的随访期内观察到的健康影响，这是迄今为止文献中最长的随访期。将接受 ivacaftor 治疗的 736 名患有门控突变（不包括 R117H）的囊性纤维化 (pwCF) 患者的队列与年龄匹配的使用 F508del 和最小功能 CFTR 变体（未使用 CFTR 调节剂）的对照组进行比较。在各队列之间观察到 FEV1 预测百分比 (ppFEV1) 存在超过 8 个百分点的差异，并且在整个队列内以及所检查的每个不同年龄组（6-11、12-17）中，差异的幅度随着时间的推移而增加。且≥18岁）。随着时间的推移，变化幅度最大的年龄段是 12 至 17 岁。在体重指数、肺部恶化率 (PEx) 和全因住院率方面观察到了伴随的益处。 ivacaftor 治疗组的肺移植率和死亡率也较低。在解释这些结果时，有两个方面很重要。首先，比较组的效度。最小功能变异的分子结果被认为与 F508del,2 和美国基于 CFFPR 的结果相似……