基因型和肺部疾病严重程度对囊性纤维化患者elexaftor -tezacaftor-ivacaftor疗效的现实影响

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics Pub Date : 2025-02-18 DOI:10.1016/j.pupt.2025.102345

Shahid Sheikh , Melissa Holtzlander , Mariah Eisner , Courtney Gushue , Sabrina Palacios , Kavitha Kotha , Sehyr Imran , Karen S. McCoy

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引用次数: 0

摘要

背景：delexaftor - tezactor -ivacaftor （ETI）治疗已显示出肺功能、BMI和肺恶化发生率的改善，但基因型和肺部疾病严重程度对ETI疗效异质性的影响尚不清楚。方法前瞻性观察性研究。对整个队列和两个亚组的基线和治疗一年的临床数据进行比较；基因型[F508del的纯合子vs杂合子]和ETI开始时肺部疾病的严重程度（ppFEV1 < 80% vs.≥80%）。结果115例pwCF患者中位年龄为23（17,32）岁，纯合子66例（58%），ppFEV1 <； 80% 76例（66%）。在整个队列中，以及基于基因型或疾病严重程度的组中，在ETI治疗一年后，观察到平均ppFEV1和平均BMI显著增加，痰/咽拭子MRSA和Pa培养阳性下降(p <；共0.05)。与ETI治疗前一年相比，在整个队列和所有四个亚组中，肺部恶化、住院次数、抗生素疗程、每日接受胸部治疗的pwCF数量、dornase α和高渗盐水均有显著改善(p <；0.05)。虽然改善并不依赖于基因型，但我们注意到，在接受ETI治疗一年后，肺部疾病更严重（ppFEV1 < 80%）的组中，ppFEV1、BMI、肺恶化和抗生素使用的平均差异更大。结论eti治疗可改善受肺部疾病严重程度影响的pwCF患者的临床预后。

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Real-life impact of genotype and severity of lung disease on efficacy of elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis

Background

Elexacaftor-tezacaftor-ivacaftor (ETI) therapy has shown improvement in lung function, BMI and reduction in pulmonary exacerbations but the impact of genotype and severity of lung disease on heterogeneity of ETI efficacy in real life is not known.

Methods

This is a prospective observational study. Clinical data at baseline and at one-year of therapy were compared for the total cohort and for two subgroups; genotype [homozygous vs. heterozygous for F508del], and severity of lung disease at ETI initiation (ppFEV₁ <80 % vs. ≥80 %).

Results

Among the total cohort of 115 pwCF, median age of 23 (17, 32) years, 66 (58 %) were homozygous, 76 (66 %) had ppFEV₁ <80 %. Significant increases in mean ppFEV₁ and mean BMI and decrease in MRSA and Pa culture positivity on sputum/throat swab were observed at one year of ETI therapy in the total cohort, and in groups based on either genotype or disease severity (p < 0.05 in all). Comparing one-year prior to one-year on ETI therapy, significant improvements were noted in pulmonary exacerbations, hospital admissions, antibiotic courses, number of pwCF receiving daily chest therapy, dornase alfa and hypertonic saline in the total cohort and in all four subgroups (p < 0.05 for all). Though improvements were not dependent on genotype, we noted larger mean differences in ppFEV₁, BMI, pulmonary exacerbations and antibiotic use in the group with more severe lung disease (ppFEV₁ <80 %) after one year of ETI therapy.

Conclusion

ETI therapy improved clinical outcomes in pwCF which were impacted by severity of underlying lung disease.

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来源期刊

Pulmonary pharmacology & therapeutics 医学-呼吸系统

CiteScore

6.20

自引率

0.00%

发文量

审稿时长

42 days

期刊介绍： Pulmonary Pharmacology and Therapeutics (formerly Pulmonary Pharmacology) is concerned with lung pharmacology from molecular to clinical aspects. The subject matter encompasses the major diseases of the lung including asthma, cystic fibrosis, pulmonary circulation, ARDS, carcinoma, bronchitis, emphysema and drug delivery. Laboratory and clinical research on man and animals will be considered including studies related to chemotherapy of cancer, tuberculosis and infection. In addition to original research papers the journal will include review articles and book reviews. Research Areas Include: • All major diseases of the lung • Physiology • Pathology • Drug delivery • Metabolism • Pulmonary Toxicology.