Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA
Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA.
BMJ Open Respir Res. 2024 Jul 29;11(1):e002033. doi: 10.1136/bmjresp-2023-002033.
Ivacaftor approval was extended to people with cystic fibrosis (CF) with ≥1 of 28 additional ivacaftor-responsive mutations in the USA in 2017 based on preclinical in vitro data. This retrospective, observational study assessed real-world clinical response to ivacaftor in people with CF with ≥1 of these mutations, using data from the US Cystic Fibrosis Foundation Patient Registry.
Participants aged ≥2 years with ≥1 of 28 eligible mutations initiating ivacaftor between May 2017 and December 2018 were included. Clinical outcomes data were evaluated for ≤1 year before and ≤2 years after ivacaftor initiation. Participants initiating ivacaftor between May and December 2017 (2017 cohort) were used for the primary analysis because up to 2 years of post-ivacaftor-initiation data were available. Analyses were descriptive; key outcomes included percent predicted forced expiratory volume in 1 s (ppFEV), body mass index (BMI) and BMI z-score, pulmonary exacerbations (PEx) and hospitalisations.
The study included 1004 eligible participants. In the 2017 cohort (n=613), mean absolute change in ppFEV from pre-ivacaftor initiation was 1.9 (95% CI 1.4, 2.4) and 1.8 (95% CI 1.0, 2.7) percentage points in years 1 and 2 post-ivacaftor initiation, respectively; mean absolute change in BMI was 0.6 (95% CI 0.5, 0.7) and 1.0 (95% CI 0.8, 1.2) kg/m in years 1 and 2, respectively; BMI z-score was unchanged. Annualised event rates of PEx and hospitalisations per patient-year were lower with ivacaftor (0.24 (95% CI 0.21, 0.26) and 0.28 (95% CI 0.25, 0.31), respectively) compared with pre-ivacaftor initiation (0.41 (95% CI 0.37, 0.46) and 0.45 (95% CI 0.41, 0.49), respectively).
These real-world observational study findings support the effectiveness of ivacaftor in people with CF aged ≥2 years with selected mutations.
2017 年，基于临床前体外数据，美国批准将依伐卡托扩大用于治疗囊性纤维化（CF）患者，这些患者至少存在 28 种额外的依伐卡托有反应的突变之一。本回顾性观察性研究使用美国囊性纤维化基金会患者登记处的数据，评估了≥2 岁、至少存在 28 种可评估突变之一的 CF 患者使用依伐卡托的真实世界临床反应。
纳入 2017 年 5 月至 2018 年 12 月期间开始使用依伐卡托的≥2 岁、至少存在 28 种可评估突变之一的患者。在依伐卡托开始使用之前的≤1 年和之后的≤2 年，评估临床结局数据。因为在依伐卡托开始使用后有长达 2 年的数据可用，所以 2017 年队列（n=613）用于主要分析。分析为描述性分析；主要结局包括预测的 1 秒用力呼气量百分比（ppFEV）、体重指数（BMI）和 BMI z 评分、肺部恶化（PEx）和住院情况。
该研究纳入了 1004 名符合条件的患者。在 2017 年队列（n=613）中，依伐卡托开始使用前，ppFEV 的绝对变化值在第 1 年和第 2 年分别为 1.9（95%CI 1.4，2.4）和 1.8（95%CI 1.0，2.7）个百分点；BMI 的绝对变化值在第 1 年和第 2 年分别为 0.6（95%CI 0.5，0.7）和 1.0（95%CI 0.8，1.2）kg/m2；BMI z 评分没有变化。与依伐卡托开始使用前相比，使用依伐卡托的患者每年 PEx 和住院治疗的年化发生率较低（分别为 0.24（95%CI 0.21，0.26）和 0.28（95%CI 0.25，0.31），和 0.41（95%CI 0.37，0.46）和 0.45（95%CI 0.41，0.49））。
这些真实世界观察性研究结果支持在≥2 岁、至少存在 28 种可评估突变之一的 CF 患者中使用依伐卡托的有效性。
