Gj Connett, S Maguire, Tc Larcombe, N Scanlan, Ss Shinde, T Muthukumarana, A Bevan, Rh Keogh, Jp Legg
National Institute for Health Research, Southampton Respiratory Biomedical Research Centre, University Hospitals Southampton NHS Foundation Trust, Southampton, UK; Southampton Children's Hospital, University Hospitals Southampton NHS Foundation Trust, Southampton, UK.
Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
Respir Med. 2025 Jan;236:107882. doi: 10.1016/j.rmed.2024.107882. Epub 2024 Nov 22.
Elexacaftor, Tezacaftor, Ivacaftor (ETI) became available in the UK in August 2020 to treat people with Cystic Fibrosis (CF) aged >12 years. We report a real-world study of clinical outcomes in young people treated with ETI at our CF centre within the first two years of its availability.
Participants aged 12-17 were identified within our clinic, with demographic data supplemented by the UK CF registry. Comprehensive outcome data spanning two years pre- and two years post-initiation of CFTR modulators were compiled from various local sources, including patient records, medication delivery logs, and clinical notes.
Of the 62 patients started on ETI (32 male, mean age 13.3 years), most (76 %) were homozygous for the F508del mutation. Three discontinuations occurred: one pregnancy, two related to side effects. Adherence was high (Proportion of Days covered >90 % both years). Following ETI initiation there was a significant increase in mean FEV1% (+11.7 units; 95 % CI 7.4-15.6), sustained throughout the two-year treatment period. There was no association between baseline lung function and the degree of improvement or rate of decline post-treatment. Improvements were similar for all treatable genotypes. BMI z-score increased by 0.25 units after four months of treatment, returning to baseline by 24 months. Intravenous antibiotic use decreased by 88 % (median IV days/year reduced from 32 to 4 days, p < 0.01).
ETI use in adolescents in a real-world setting led to sustained improvements in health outcomes, consistent with those seen in open trial extension studies.
依列卡福妥、替扎卡福妥、依伐卡托（ETI）于2020年8月在英国上市，用于治疗12岁以上的囊性纤维化（CF）患者。我们报告了一项在ETI上市的头两年内，在我们的CF中心接受治疗的年轻人临床结局的真实世界研究。
在我们的诊所中识别出年龄在12 - 17岁的参与者，人口统计学数据由英国CF登记处补充。从各种本地来源收集了CFTR调节剂开始使用前两年和开始使用后两年的综合结局数据，包括患者记录、药物递送日志和临床笔记。
在开始使用ETI的62例患者中（32例男性，平均年龄13.3岁），大多数（76%）为F508del突变纯合子。发生了3例停药：1例因怀孕，2例与副作用有关。依从性很高（两年的日覆盖比例均>90%）。开始使用ETI后，平均FEV1%显著增加（+11.7个单位；95%置信区间7.4 - 15.6），在整个两年治疗期内持续存在。基线肺功能与治疗后改善程度或下降速率之间无关联。所有可治疗基因型的改善情况相似。治疗四个月后BMI z评分增加了0.25个单位，到24个月时恢复到基线水平。静脉使用抗生素减少了88%（每年静脉使用天数中位数从32天降至4天，p < 0.01）。
在真实世界环境中，青少年使用ETI可使健康结局持续改善，与开放试验扩展研究中的情况一致。
