WS12.05Change in pancreatic status in children aged 2-5 years after initiation of elexacaftor/tezacaftor/ivacaftor

IF 5.4 2区医学 Q1 RESPIRATORY SYSTEM

Journal of Cystic Fibrosis Pub Date : 2025-06-01 DOI:10.1016/j.jcf.2025.03.562

P. Roper , E. Owen , R. Brugha

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引用次数: 0

Abstract

Objectives

CFTR modulators may improve or restore pancreatic function in young children(1). We sought to explore changes in Faecal Elastase (FE-1) and Pancreatic Enzyme Replacement Therapy (PERT) in a real-world population of children aged 2-5 years after initiation of Elexacaftor/Tezacaftor/Ivacaftor (ETI).

Methods

A prospective data collection was performed in Pancreatic Insufficient (PI) children at our centre, aged 2-5 years, at baseline and three months post initiation of ETI. We collected FE-1, PERT dose, genotype, prior modulator use, and anthropometry. PI was classified as (µg/g stool): <100 severe, 100-200 moderate, >200 Pancreatic Sufficient (PS). High PERT dose (units/lipase/kg/day) >10,000 as per ECFS guideline(2). Moderate PERT dose classified as 3,000-9,999, <3,000 low dose. Data were analysed using R 4.4.2, comparisons by Wilcoxon signed rank test and Chi-squared test.

Results

Twenty nine children were included, 18 homozygous dF508, 11 heterozygous dF508, 12 were Modulator-Naïve (MN). Mean (sd) age 4.1 (1.1)y at ETI initiation, BMI z-score 0.22(0.8). Paired FE-1 (median, IQR) was obtained in 28 children and increased from 15(0) µg/g to 15(4) µg/g, p=0.057. Categorical PERT doses were not significantly reduced (p=0.061), 5 children reduced from high to moderate, 4 children reduced from moderate to low, and 1 child became PS (not MN).

Conclusions

We demonstrate a small increase in FE-1 in the 2-5 year old children in our centre three months after starting ETI. PERT doses were not reduced. Our findings should be interpreted in the context of a small study size, risk of type I error, and the subjective nature of recording PERT administration. These data may add to the emerging evidence that early life administration of ETI has the potential to modify pancreatic function. Iterative data collection is ongoing in our centre.

1. Davies JC et al. Lancet Resp Med 2016

2. Wilschanski M et al. Clin Nutr 2024

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2-5岁儿童开始使用elexaftor /tezacaftor/ivacaftor后胰腺状态的变化

目的cftr调节剂可改善或恢复幼儿胰腺功能(1)。我们试图探索在现实世界2-5岁儿童人群中开始使用Elexacaftor/Tezacaftor/Ivacaftor （ETI）后粪便弹性酶（FE-1）和胰酶替代疗法（PERT）的变化。方法对我院2-5岁胰腺功能不全（PI）患儿进行前瞻性数据收集，分别为基线和ETI开始后3个月。我们收集了FE-1、PERT剂量、基因型、既往调节剂使用和人体测量数据。PI分为（µg/g粪便）：严重≤100，中度≤100，胰足≤200 （PS）。高PERT剂量（单位/脂肪酶/kg/天）&根据ECFS指南10,000(2)。中度PERT剂量为3000 - 9999，低剂量为3000。数据分析采用r4.4.2，比较采用Wilcoxon符号秩检验和卡方检验。结果29例患儿中，纯合子dF508 18例，杂合子dF508 11例，Modulator-Naïve (MN) 12例。ETI开始时的平均（sd）年龄为4.1（1.1）岁，BMI z-score为0.22（0.8）。28名儿童获得配对FE-1（中位数，IQR），从15(0)µg/g增加到15(4)µg/g, p=0.057。分类PERT剂量没有显著降低（p=0.061）， 5名儿童从高剂量降至中度，4名儿童从中度降至低剂量，1名儿童变为PS（非MN）。我们发现，在我们中心开始ETI三个月后，2-5岁儿童的FE-1有小幅增加。PERT剂量没有减少。我们的研究结果应该在小研究规模、I型错误风险和记录PERT给药的主观性的背景下进行解释。这些数据可能增加了早期给予ETI有可能改变胰腺功能的新证据。我们中心正在进行反复的数据收集。Davies JC等。Lancet Resp Med 20162。Wilschanski M等。克林·诺尔2024

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来源期刊

Journal of Cystic Fibrosis 医学-呼吸系统

CiteScore

10.10

自引率

13.50%

发文量

1361

审稿时长

50 days

期刊介绍： The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.