University Hospital of South Manchester NHS Foundation Trust, Manchester, England.
University Hospital of South Manchester NHS Foundation Trust, Manchester, England; Royal College of Physicians of Ireland, Dublin, Ireland; Cork University Hospital, University College Cork, Cork, Ireland.
Chest. 2014 Jul;146(1):152-158. doi: 10.1378/chest.13-2397.
The development of ivacaftor represents a significant advance in therapeutics for patients with cystic fibrosis (CF) who carry the G551D mutation. Patients with an FEV1 < 40% predicted represent a considerable proportion of eligible patients but were excluded from phase 3 clinical trials, and the effectiveness of the drug in this population is, therefore, unknown.
Data were collected from adult CF centers in the United Kingdom and Ireland with patients enrolled in an ivacaftor compassionate use program (FEV1 < 40% or on lung transplant waiting list). Clinically recorded data were collated from patient records for 1 year prior and for a period of 90 to 270 days following ivacaftor commencement. Each patient was matched to two control subjects who would have met the requirements for the compassionate use program with the exception of genotype.
Twenty-one patients received ivacaftor for a median of 237 days. Mean FEV1 improved from 26.5% to 30.7% predicted (P = .01), representing a 16.7% relative improvement. Median weight improved from 49.8 to 51.6 kg (P = .006). Median inpatient IV antibiotic days declined from 23 to 0 d/y (P = .001) and median total IV treatment days decreased from 74 to 38 d/y (P = .002) following ivacaftor. Changes in pulmonary function and IV antibiotic requirements were significant compared with control subjects.
Ivacaftor was clinically effective in patients with CF who carry the G551D mutation and have severe pulmonary disease. The reductions in treatment requirements were clinically and statistically significant and have not been described in less severe populations.
依伐卡托的研发是囊性纤维化（CF）治疗领域的重大进展，它适用于携带 G551D 突变的患者。FEV1<40%预计值的患者占符合条件患者的相当大比例，但被排除在 3 期临床试验之外，因此，该药在这一人群中的疗效尚不清楚。
数据来自英国和爱尔兰的成人 CF 中心，这些患者参加了依伐卡托同情用药项目（FEV1<40%或在肺移植等待名单上）。从患者记录中收集了依伐卡托开始使用前 1 年和使用后 90 至 270 天的临床记录数据。每个患者都与两名对照者相匹配，这些对照者除了基因型外，都符合同情用药项目的要求。
21 名患者接受依伐卡托治疗，中位数为 237 天。FEV1 平均值从 26.5%提高到 30.7%预计值（P=0.01），相对改善 16.7%。中位体重从 49.8 千克增加到 51.6 千克（P=0.006）。依伐卡托治疗后，中位住院 IV 抗生素天数从 23 天降至 0 天/年（P=0.001），中位总 IV 治疗天数从 74 天降至 38 天/年（P=0.002）。与对照组相比，肺功能和 IV 抗生素需求的变化具有统计学意义。
依伐卡托对携带 G551D 突变且患有严重肺部疾病的 CF 患者具有临床疗效。治疗需求的减少具有临床和统计学意义，在病情较轻的人群中尚未描述。
