Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del
Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del
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DOI：
10.1056/nejmoa1709846
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发表时间：
2017-11-23
影响因子：
158.5
通讯作者：
Elborn, J. Stuart
中科院分区：
文献类型：
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作者：
Taylor-Cousar, Jennifer L.;Munck, Anne;Elborn, J. Stuart
背景囊性纤维化跨膜传导调节因子（CFTR）调节剂替扎卡托（VX-661）和依伐卡托（VX-770）的联合治疗旨在针对囊性纤维化患者的潜在病因。我们在12岁或以上患有囊性纤维化并且CFTR Phe 508 del突变纯合子的患者中评估了替扎卡托和依伐卡托的联合治疗。患者以1：1的比例随机分配接受100 mg替扎卡托每日一次和150 mg依伐卡托每日两次或匹配的安慰剂治疗24周。主要终点为第24周时1秒用力呼气量（FEV 1）预测值百分比的绝对变化（以百分比计算）;至第24周FEV 1预测值百分比的相对变化在随机分组的510名患者中，509名接受了替扎卡托-依伐卡托或安慰剂，475人完成了24周的试验方案。基线时的平均FEV 1为预测值的60.0%。与安慰剂相比，替扎卡托-依伐卡托对预测的FEV 1百分比的绝对和相对变化的影响分别为4.0个百分点和6.8%（P
BACKGROUNDCombination treatment with the cystic fibrosis transmembrane conductance regulator (CFTR) modulators tezacaftor (VX-661) and ivacaftor (VX-770) was designed to target the underlying cause of disease in patients with cystic fibrosis.METHODSIn this phase 3, randomized, double-blind, multicenter, placebo-controlled, parallel-group trial, we evaluated combination therapy with tezacaftor and ivacaftor in patients 12 years of age or older who had cystic fibrosis and were homozygous for the CFTR Phe508del mutation. Patients were randomly assigned in a 1:1 ratio to receive either 100 mg of tezacaftor once daily and 150 mg of ivacaftor twice daily or matched placebo for 24 weeks. The primary end point was the absolute change in the percentage of the predicted forced expiratory volume in 1 second (FEV1) through week 24 (calculated in percentage points); relative change in the percentage of the predicted FEV1 through week 24 (calculated as a percentage) was a key secondary end point.RESULTSOf the 510 patients who underwent randomization, 509 received tezacaftor-ivacaftor or placebo, and 475 completed 24 weeks of the trial regimen. The mean FEV1 at baseline was 60.0% of the predicted value. The effects on the absolute and relative changes in the percentage of the predicted FEV1 in favor of tezacaftor-ivacaftor over placebo were 4.0 percentage points and 6.8%, respectively (P