Background

Ivacaftor is an innovative treatment for CF. Ivacaftor monotherapy in a phase III trial for patients with F508del and a residual function (RF) mutation showed improvement in lung function. We evaluated the effectiveness and safety of ivacaftor in patients with severe CF carrying RF mutations.

Methods

Data were collected from Italian CF centers with patients enrolled in an ivacaftor compassionate use program. Data were collected 1 year before and 1 year after commencement of ivacaftor.

Results

Twenty-six patients received ivacaftor. The mean [standard deviation (SD)] percent predicted FEV₁ significantly increased from 33.9% (8.3) before treatment to 44.0% (10.7) after 12 months of treatment (p < 0.00001). The mean distance in the 6-min walking-test significantly improved from 458.2 (110.5) m at baseline to 524.8 (91.9) m after 12 months (p < 0.00001). The overall number of days of antibiotic therapy decreased from 1693 during the year before ivacaftor to 714 in the year following ivacaftor, and the number of days of intravenous antibiotic treatment dropped from 714 to 88; both results were statistically significant (p < 0.00001). Patients needing intravenous therapy decreased from 23 to 5 of 26. The mean (SD) sweat chloride level decreased from a baseline of 79 (22.3) mmol/L to 65 (30.6) mmol/L, but this variation was not significant (p = 0.26). No safety concerns were registered.

Conclusions

In patients with CFTR mutations that confer RF with severe lung disease, treatment with Ivacaftor is safe and results in a clinically significant improvement that was evident at 1 month and maintained at 12 months.

中文翻译：

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依伐卡托可改善携带CFTR突变并赋予残余功能的晚期CF患者的肺部疾病。

背景

Ivacaftor是CF的创新疗法。Ivacaftor单一疗法在F508del和残留功能（RF）突变患者的III期试验中显示肺功能得到改善。我们评估了依伐卡托对伴有RF突变的严重CF患者的有效性和安全性。

方法

数据从意大利CF中心收集，患者参加了ivacaftor富有同情心的使用计划。在ivacaftor开始前1年和1年后收集数据。

结果

26例患者接受了依伐卡托治疗。预测FEV ₁的平均[标准偏差（SD）]百分比从治疗前的33.9％（8.3）显着增加到治疗12个月后的44.0％（10.7）（p <0.00001）。6分钟步行测试中的平均距离从基线时的458.2（110.5）m显着提高到12个月后的524.8（91.9）m（p <0.00001）。抗生素治疗的总天数从依伐卡托之前的1693天减少到依伐卡托之后的714天，静脉内抗生素治疗的天数从714天减少到88天。两项结果均具有统计学意义（p <0.00001）。需要静脉注射治疗的患者从23人减少到26人中的5人。平均（SD）汗液氯化物水平从基线的79（22.3）mmol / L降低到65（30.6）mmol / L，但这种变化并不明显（p = 0.26）。没有注册安全隐患。

结论

对于具有RF导致严重肺部疾病的CFTR突变的患者，使用Ivacaftor治疗是安全的，并导致临床上的显着改善，这种改善在1个月时可见，并在12个月时保持。