Sagel Scott D, Khan Umer, Heltshe Sonya L, Clancy John P, Borowitz Drucy, Gelfond Daniel, Donaldson Scott H, Moran Antoinette, Ratjen Felix, VanDalfsen Jill M, Rowe Steven M
Department of Pediatrics, Children's Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, Washington.
Ann Am Thorac Soc. 2021 Jan;18(1):75-83. doi: 10.1513/AnnalsATS.202002-144OC.
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. To evaluate the effectiveness of LUM/IVA in children (6 yr or more) and adults (more than 18 yr) in a postapproval setting. 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. 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) was 85 (standard deviation, 22.4) in this cohort. No statistically significant change in ppFEV 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; < 0.001). Sweat chloride decreased from baseline to 1 month (mean change, -18.5 mmol/L; 95% CI, -20.7 to -16.3; < 0.001), and these reductions were sustained through the study period. There were no significant changes in hospitalization rate for pulmonary exacerbations and infection status with treatment. 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 infection.Clinical trial registered with www.clinicaltrials.gov (NCT02477319).
鲁玛卡托（LUM）和依伐卡托（IVA）联合用药是一种已获批准的用于治疗纯合子F508del型囊性纤维化（CF）患者的CFTR（囊性纤维化跨膜传导调节因子）调节剂。为了评估LUM/IVA在批准后环境中对儿童（6岁及以上）和成人（18岁以上）的有效性。这项纵向队列研究在美国CF治疗发展网络的38个中心进行，纳入了年龄在6岁及以上、此前未接触过LUM/IVA的纯合子F508del型CF患者。在基线以及开始使用LUM/IVA后的1、3、6和12个月进行研究评估。共有193名患者开始使用LUM/IVA，85%的患者完成了1年的研究。该队列中，基线时1秒用力呼气容积预测值百分比（ppFEV）的平均值为85（标准差，22.4）。从基线到任何随访时间点，均未观察到ppFEV有统计学意义的变化，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）。体重指数从基线到12个月有所改善（平均变化，0.8kg/m²；P＜0.001）。汗液氯化物从基线到1个月有所下降（平均变化，-18.5mmol/L；95%CI，-20.7至-16.3；P＜0.001），且这些下降在研究期间持续存在。肺部加重的住院率和治疗后的感染状况无显著变化。在这个现实世界中的多中心儿童和成人队列中，LUM/IVA治疗与生长的显著改善和汗液氯化物的降低相关，而肺功能、住院率或感染方面无统计学意义或临床意义的变化。在www.clinicaltrials.gov注册的临床试验（NCT02477319）。
