BACKGROUND Phase 3 trials have demonstrated the safety and efficacy of lumacaftor-ivacaftor (LUMA-IVA) in patients with cystic fibrosis (CF) homozygous for the Phe508del CFTR mutation and percent predicted forced expiratory volume in 1 s (ppFEV1) between 40 and 90. Marketing authorizations have been granted for patients at all levels of ppFEV1. METHODS To evaluate the safety and effectiveness of LUMA-IVA over the first year of treatment in patients with ppFEV1<40 or ppFEV1≥90 in comparison with those with ppFEV1 [40-90[. Analysis of data collected during a real world study, which included all patients aged ≥12 years who started LUMA-IVA in 2016 across all 47 French CF centers. RESULTS 827 patients were classified into 3 subgroups according to ppFEV1 at treatment initiation (ppFEV1<40, n = 121; ppFEV1 [40-90[, n = 609; ppFEV1≥90, n = 97). Treatment discontinuation rate was higher in ppFEV1<40 patients (28.9%) than in those with ppFEV1 [40-90[(16.4%) or ppFEV1≥90 (17.5%). In patients with uninterrupted treatment, significant increase in ppFEV1 occurred in the ppFEV1 [40-90[subgroup (+2.9%, P<0.001), and in those ppFEV1<40 (+0.5%, P = 0.03) but not in those with ppFEV1≥90 (P = 0.46). Compared with the year prior to initiation, the number of days of intravenous antibiotics were reduced in all subgroups, although 72% of patients with ppFEV1<40 still experienced at least one exacerbation/year under LUMA-IVA. Comparable increase in body mass index was seen in the three subgroups. CONCLUSION Phe508del homozygous CF patients benefit from LUMA-IVA at all levels of baseline lung function, but the characteristics and magnitude of the response vary depending on ppFEV1 at baseline.

中文翻译：

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根据基线肺功能，囊性纤维化患者对 lumacaftor-ivacaftor 的临床反应

背景 3 期试验已经证明了 lumacaftor-ivacaftor (LUMA-IVA) 在 Phe508del CFTR 突变纯合子囊性纤维化 (CF) 患者中的安全性和有效性，并且预测的 1 秒用力呼气量百分比 (ppFEV1) 在 40 到 90 之间。 ppFEV1各级患者均已获得上市许可。方法 与 ppFEV1 [40-90[. 分析在现实世界研究中收集的数据，其中包括所有 47 个法国 CF 中心于 2016 年开始使用 LUMA-IVA 的年龄≥12 岁的所有患者。结果 827 名患者根据治疗开始时的 ppFEV1 分为 3 个亚组（ppFEV1<40，n = 121；ppFEV1 [40-90[，n = 609；ppFEV1≥90，n = 97）。ppFEV1<40 患者 (28.9%) 的治疗中断率高于 ppFEV1 [40-90[(16.4%) 或 ppFEV1≥90 (17.5%) 的患者。在不间断治疗的患者中，ppFEV1 [40-90[亚组 (+2.9%, P<0.001) 和 ppFEV1<40 (+0.5%, P = 0.03) 的患者中 ppFEV1 显着增加，但没有ppFEV1≥90 (P = 0.46)。与开始前一年相比，所有亚组的静脉注射抗生素天数都减少了，尽管 72% 的 ppFEV1<40 的患者在 LUMA-IVA 下仍经历至少一次恶化/年。在三个亚组中观察到体重指数的可比增加。结论 Phe508del 纯合子 CF 患者在所有基线肺功能水平均受益于 LUMA-IVA，但反应的特征和幅度因基线 ppFEV1 而异。