Schütz Katharina, Pallenberg Sophia Theres, Kontsendorn Julia, DeLuca David, Sukdolak Cinja, Minso Rebecca, Büttner Tina, Wetzke Martin, Dopfer Christian, Sauer-Heilborn Annette, Ringshausen Felix C, Junge Sibylle, Tümmler Burkhard, Hansen Gesine, Dittrich Anna-Maria
Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research, Hannover Medical School, Hannover, Germany.
Front Pharmacol. 2023 Jul 4;14:1171544. doi: 10.3389/fphar.2023.1171544. eCollection 2023.
Triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ETI) was introduced in August 2020 in Germany for people with CF (pwCF) ≥12 years (yrs.) of age and in June 2021 for pwCF ≥6 yrs of age. In this single-center study, we analyzed longitudinal data on the percent-predicted forced expiratory volume (ppFEV1) and body-mass-index (BMI) for 12 months (mo.) after initiation of ETI by linear mixed models and regression analyses to identify age- and severity-dependent determinants of response to ETI. We obtained data on 42 children ≥6-11 yrs, 41 adolescents ≥12-17 yrs, and 143 adults by spirometry and anthropometry prior to ETI, and 3 and 12 mo. after ETI initiation. Data were stratified by the age group and further sub-divided into age-specific ppFEV1 impairment. To achieve this, the age strata were divided into three groups, each according to their baseline ppFEV1: lowest 25%, middle 50%, and top 25% of ppFEV1. Adolescents and children with more severe lung disease prior to ETI (within the lowest 25% of age-specific ppFEV1) showed higher improvements in lung function than adults in this severity group (+18.5 vs. +7.5; = 0.002 after 3 mo. and +13.8 vs. +7.2; = 0.012 after 12 mo. of ETI therapy for ≥12-17 years and +19.8 vs. +7.5; = 0.007 after 3 mo. for children ≥6-11 yrs). In all age groups, participants with more severe lung disease showed higher BMI gains than those with medium or good lung function (within the middle 50% or top 25% of age-specific ppFEV1). Regression analyses identified age as a predictive factor for FEV1 increase at 3 mo. after ETI initiation, and age and ppFEV1 at ETI initiation as predictive factors for FEV1 increase 12 mo. after ETI initiation. We report initial data, which suggest that clinical response toward ETI depends on age and lung disease severity prior to ETI initiation, which argue for early initiation of ETI.
三联组合囊性纤维化跨膜传导调节因子（CFTR）调节剂疗法依列卡托/替扎卡托/依伐卡托（ETI）于2020年8月在德国被引入用于年龄≥12岁的囊性纤维化患者（pwCF），并于2021年6月用于年龄≥6岁的pwCF。在这项单中心研究中，我们通过线性混合模型和回归分析，分析了ETI开始治疗后12个月内预测用力呼气量百分比（ppFEV1）和体重指数（BMI）的纵向数据，以确定对ETI反应的年龄和严重程度依赖性决定因素。我们在ETI治疗前、治疗开始后3个月和12个月，通过肺活量测定法和人体测量法获取了42名6至11岁儿童、41名12至17岁青少年和143名成年人的数据。数据按年龄组分层，并进一步细分为特定年龄的ppFEV1损伤情况。为实现这一点，年龄层根据其基线ppFEV1分为三组：ppFEV1最低的25%、中间的50%和最高的25%。在ETI治疗前肺部疾病更严重的青少年和儿童（在特定年龄ppFEV1的最低25%范围内），在该严重程度组中，其肺功能改善程度高于成年人（3个月后为+18.5对+7.5；P = 0.002，12个月后为+13.8对+7.2；P = 0.012，对于12至17岁患者ETI治疗12个月后为+19.8对+7.5；P = 0.007，对于6至11岁儿童3个月后）。在所有年龄组中，肺部疾病更严重的参与者比肺功能中等或良好的参与者（在特定年龄ppFEV1的中间50%或最高25%范围内）体重指数增加更高。回归分析确定年龄是ETI开始治疗后3个月FEV1增加的预测因素，而ETI开始治疗时的年龄和ppFEV1是ETI开始治疗后12个月FEV1增加的预测因素。我们报告了初步数据，表明对ETI的临床反应取决于ETI开始治疗前的年龄和肺部疾病严重程度，这支持尽早开始ETI治疗。
