Clinical Effectiveness of Lumacaftor/Ivacaftor in Patients with Cystic Fibrosis Homozygous for F508del-CFTR A Clinical Trial
Clinical Effectiveness of Lumacaftor/Ivacaftor in Patients with Cystic Fibrosis Homozygous for F508del-CFTR A Clinical Trial
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DOI：
10.1513/annalsats.202002-144oc
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发表时间：
2021-01-01
影响因子：
8.3
通讯作者：
Rowe, Steven M.
中科院分区：
文献类型：
--
作者：
Sagel, Scott D.;Khan, Umer;Rowe, Steven M.
基本原理：Lumacaftor（LUM）和ivacaftor（IVA）的组合是批准的CFTR目的：评价LUM/IVA治疗儿童囊性纤维化（CF）的有效性（6岁或以上）和成人（18岁以上）在批准后的环境中。方法：这项纵向队列研究在美国CF治疗开发网络的38个中心进行，入组6岁及以上、既往未暴露于LUM/IVA的CF纯合子F508 del患者。研究评估进行了基线和1，3，6，和12个月后LUM/IVA initiation.Results：共有193例患者启动LUM/IVA，85%完成了研究，通过1年。在该队列中，基线时平均每秒钟预测用力呼气量（ppFEV（1））为85（标准差，22.4）。从基线到任何随访时间点，未观察到ppFEV 1的统计学显著变化，12个月时的平均绝对变化为-0.3（95%置信区间[CI]，-1.8至1.2）。从基线到12个月，体重指数改善（平均变化，0.8 kg/m2; P < 0.001）。从基线到1个月，汗液氯化物降低（平均变化，-18.5 mmol/L; 95% CI，-20.7至-16.3; P < 0.001），并且这些降低在整个研究期间持续。有没有显着的变化，在住院率为肺部急性加重和铜绿假单胞菌感染状态与treatment.Conclusions：在这个现实世界的多中心队列的儿童和成人，LUM/IVA治疗与显着改善生长和减少汗液氯化物没有统计学意义或临床意义的变化，肺功能，住院率，或铜绿假单胞菌感染。
Rationale: The combination of lumacaftor (LUM) and ivacaftor (IVA) is an approved CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator treatment for homozygous F508del patients with CF.Objectives: To evaluate the effectiveness of LUM/IVA in children (6 yr or more) and adults (more than 18 yr) in a postapproval setting.Methods: This longitudinal cohort study, performed at 38 centers in the U.S. CF Therapeutics Development Network, enrolled homozygous F508del patients with CF ages 6 years old and older with no prior exposure to LUM/IVA. Study assessments were performed at baseline and at 1, 3, 6, and 12 months after LUM/IVA initiation.Results: A total of 193 patients initiated LUM/IVA, and 85% completed the study through 1 year. Baseline mean percent-predicted forced expiratory volume in 1 second (ppFEV(1)) was 85 (standard deviation, 22.4) in this cohort. No statistically significant change in ppFEV1 was observed from baseline to any of the follow-up time points, with a mean absolute change at 12 months of -0.3 (95% confidence interval [CI], -1.8 to 1.2). Body mass index improved from baseline to 12 months (mean change, 0.8 kg/m(2); P < 0.001). Sweat chloride decreased from baseline to 1 month (mean change, -18.5 mmol/L; 95% CI, -20.7 to -16.3; P < 0.001), and these reductions were sustained through the study period. There were no significant changes in hospitalization rate for pulmonary exacerbations and Pseudomonas aeruginosa infection status with treatment.Conclusions: In this real-world multicenter cohort of children and adults, LUM/IVA treatment was associated with significant improvements in growth and reductions in sweat chloride without statistically significant or clinically meaningful changes in lung function, hospitalization rates, or P. aeruginosa infection.