Zwitserloot A M, Aziz S Z, Chen Y, Bannier M A G E, Janssens H M, Merkus P F J M, Nuijsink M, Terheggen-Lagro S W J, Tiddens H A W M, Zomer-van Ommen D D, Vonk J M, de Winter-de Groot K M, Willemse B W M, Koppelman G H
Beatrix Children's Hospital Department of Pediatric Pulmonology and Pediatric Allergy, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.
Pediatr Pulmonol. 2025 Jan;60(1):e27473. doi: 10.1002/ppul.27473.
Lumacaftor/ivacaftor (lum/iva) was introduced in the Netherlands in 2017. We investigated 1-year efficacy of lum/iva on lung function and small airway and structural lung disease evaluated by multiple breath nitrogen washout and CT scan. Additionally, we investigated effects of lum/iva on exacerbations, anthropometry, sweat chloride and safety in children with CF in the Netherlands.
Children with CF aged 6-18 years and homozygous for F508del treated in one of the seven Dutch CF centers for at least 12 months were eligible. Data were extracted from the Dutch CF Registry and electronic patient records. Primary outcome was change in percent predicted FEV (ppFEV) after 12 months.
Nationwide, 247 children with CF were eligible for lum/iva. Eight patients discontinued lum/iva due to side effects. In total, 223/247 children (90.3%) were evaluated. Mean (range) age at baseline was 11.0 (6.0-17.1) years. There was no change in FEV after 12 months of lum/iva. In a subgroup, markers of small airway function and structural lung disease, such as LCI (n = 28), mean change (SD) -10.0% (15.8), and bronchus-artery (BA) analysis on CT scan (n = 81), showed significant improvement (p < 0.01). Moreover, BMI (n = 192), exacerbations (n = 219) and sweat chloride measurements (n = 105) improved.
Lum/iva was generally well tolerated in a real-life, nationwide pediatric cohort. The efficacy of lum/iva was comparable to phase 3 studies in children. LCI and BA analysis as markers of small airway and structural lung disease showed significant improvement which indicates the importance of these parameters to evaluate treatment effects of CF modulators in children.
鲁马卡托/依伐卡托（lum/iva）于2017年在荷兰上市。我们研究了lum/iva对肺功能、小气道和肺部结构疾病的1年疗效，这些指标通过多次呼吸氮洗脱和CT扫描进行评估。此外，我们还研究了lum/iva对荷兰囊性纤维化（CF）儿童病情加重、人体测量、汗液氯化物水平及安全性的影响。
年龄在6至18岁、F508del纯合子且在荷兰七个CF中心之一接受治疗至少12个月的CF儿童符合条件。数据从荷兰CF登记处和电子病历中提取。主要结局是12个月后预测第一秒用力呼气容积百分比（ppFEV）的变化。
在全国范围内，247名CF儿童符合使用lum/iva的条件。8名患者因副作用停用lum/iva。总共对223/247名儿童（90.3%）进行了评估。基线时的平均（范围）年龄为11.0（6.0 - 17.1）岁。使用lum/iva 12个月后，FEV没有变化。在一个亚组中，小气道功能和肺部结构疾病的标志物，如肺清除指数（LCI，n = 28），平均变化（标准差）为 -10.0%（15.8），以及CT扫描的支气管 - 动脉（BA）分析（n = 81）显示有显著改善（p < 0.01）。此外，体重指数（BMI，n = 192）、病情加重情况（n = 219）和汗液氯化物测量值（n = 105）均有所改善。
在一个真实的全国性儿科队列中，lum/iva总体耐受性良好。lum/iva的疗效与儿童3期研究相当。LCI和BA分析作为小气道和肺部结构疾病的标志物显示有显著改善，这表明这些参数对于评估CF调节剂在儿童中的治疗效果具有重要意义。
