Elexacaftor/tezacaftor/ivacaftor，囊性纤维化领域的变革者：葡萄牙的经验

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics Pub Date : 2024-09-17 DOI:10.1016/j.pupt.2024.102328

E. Fragoso , R. Boaventura , L. Almeida , A. Amorim , F. Gamboa , A.S. Santos , F. Gonçalves , C.M. Cruz , A. Carreiro , A.S. Gonçalves , V. Teixeira , P. Azevedo

{"title":"Elexacaftor/tezacaftor/ivacaftor，囊性纤维化领域的变革者：葡萄牙的经验","authors":"E. Fragoso , R. Boaventura , L. Almeida , A. Amorim , F. Gamboa , A.S. Santos , F. Gonçalves , C.M. Cruz , A. Carreiro , A.S. Gonçalves , V. Teixeira , P. Azevedo","doi":"10.1016/j.pupt.2024.102328","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Phase 3 trials of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) combination treatment in people with cystic fibrosis (CF) with ≥1 <em>F508del-CFTR</em> allele showed profound short-term effects on lung function, weight, and pulmonary exacerbations (PEx). The authors conducted a 12-month study to add evidence on the real-world long-term effectiveness and safety of CFTR modulator therapy with ELX/TEZ/IVA in Portuguese CF adult population.</p></div><div><h3>Methods</h3><p>Ambispective, multicentre, observational, real-life study involving all the Portuguese CF Reference Centres. Adult patients on treatment with ELX/TEZ/IVA combination outside clinical trials were included. Demographics, efficacy, and safety variables on the first 12 months of treatment were compared with the pre-treatment year.</p></div><div><h3>Results</h3><p>132 adult people with CF were included, of which 119 completed 12 months treatment (mean duration of treatment 21.5 months). Mean age was 31.7 ± 11.0 years, 53 % patients were homozygous for the <em>F508del</em> variant, baseline sweat chloride was 86.7 ± 25.9 mmol/L and pre-treatment percent-predicted FEV<sub>1</sub> was 77.9 ± 19.7 %. At 1 year, mean absolute change from baseline in FEV<sub>1</sub> was +0.46L (95 % CI: 0.37, 0.55; p < 0.001) and +13.9 percentage points (95 % CI: 11.5, 16.2; p < 0.001). PEx episodes decreased by 78 % (p < 0.001) and hospitalizations for PEx decreased by 91.4 % (p < 0.001). Body mass index (BMI) increased 1.2 kg/m<sup>2</sup> (95 % CI: 0.9, 1.5; p < 0.001). Mean sweat chloride variation was −44.5 mmol/L (95 % CI: −49.8, −39.2; p < 0.001). No correlation was found between sweat chloride and lung function (r = −0.116, p = 0.335). There were no major safety concerns. Of note, headache was reported in 7.6 % and neuropsychiatric manifestations occurred in 12.6 % treated patients, being anxiety and depressive disorders the most common.</p></div><div><h3>Conclusions</h3><p>ELX/TEZ/IVA treatment in Portuguese adults with CF was associated with significant improvement in lung function, a drop in PEx and PEx-related hospitalizations and increase in BMI at 12 months and was well tolerated. These results add knowledge to our understanding of clinical benefits and tolerability of ELX/TEZ/IVA. Careful evaluation of adverse effects of ELX/TEZ/IVA therapy and its determinants, mainly concerning mental health, are a research priority.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102328"},"PeriodicalIF":3.3000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Elexacaftor/tezacaftor/ivacaftor, a game-changer in cystic fibrosis: The Portuguese experience\",\"authors\":\"E. Fragoso , R. Boaventura , L. Almeida , A. Amorim , F. Gamboa , A.S. Santos , F. Gonçalves , C.M. Cruz , A. Carreiro , A.S. Gonçalves , V. Teixeira , P. Azevedo\",\"doi\":\"10.1016/j.pupt.2024.102328\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Phase 3 trials of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) combination treatment in people with cystic fibrosis (CF) with ≥1 <em>F508del-CFTR</em> allele showed profound short-term effects on lung function, weight, and pulmonary exacerbations (PEx). The authors conducted a 12-month study to add evidence on the real-world long-term effectiveness and safety of CFTR modulator therapy with ELX/TEZ/IVA in Portuguese CF adult population.</p></div><div><h3>Methods</h3><p>Ambispective, multicentre, observational, real-life study involving all the Portuguese CF Reference Centres. Adult patients on treatment with ELX/TEZ/IVA combination outside clinical trials were included. Demographics, efficacy, and safety variables on the first 12 months of treatment were compared with the pre-treatment year.</p></div><div><h3>Results</h3><p>132 adult people with CF were included, of which 119 completed 12 months treatment (mean duration of treatment 21.5 months). Mean age was 31.7 ± 11.0 years, 53 % patients were homozygous for the <em>F508del</em> variant, baseline sweat chloride was 86.7 ± 25.9 mmol/L and pre-treatment percent-predicted FEV<sub>1</sub> was 77.9 ± 19.7 %. At 1 year, mean absolute change from baseline in FEV<sub>1</sub> was +0.46L (95 % CI: 0.37, 0.55; p < 0.001) and +13.9 percentage points (95 % CI: 11.5, 16.2; p < 0.001). PEx episodes decreased by 78 % (p < 0.001) and hospitalizations for PEx decreased by 91.4 % (p < 0.001). Body mass index (BMI) increased 1.2 kg/m<sup>2</sup> (95 % CI: 0.9, 1.5; p < 0.001). Mean sweat chloride variation was −44.5 mmol/L (95 % CI: −49.8, −39.2; p < 0.001). No correlation was found between sweat chloride and lung function (r = −0.116, p = 0.335). There were no major safety concerns. Of note, headache was reported in 7.6 % and neuropsychiatric manifestations occurred in 12.6 % treated patients, being anxiety and depressive disorders the most common.</p></div><div><h3>Conclusions</h3><p>ELX/TEZ/IVA treatment in Portuguese adults with CF was associated with significant improvement in lung function, a drop in PEx and PEx-related hospitalizations and increase in BMI at 12 months and was well tolerated. These results add knowledge to our understanding of clinical benefits and tolerability of ELX/TEZ/IVA. Careful evaluation of adverse effects of ELX/TEZ/IVA therapy and its determinants, mainly concerning mental health, are a research priority.</p></div>\",\"PeriodicalId\":20799,\"journal\":{\"name\":\"Pulmonary pharmacology & therapeutics\",\"volume\":\"87 \",\"pages\":\"Article 102328\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-09-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pulmonary pharmacology & therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1094553924000440\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pulmonary pharmacology & therapeutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1094553924000440","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

摘要

背景Elexacaftor/tezacaftor/ivacaftor（ELX/TEZ/IVA）联合治疗≥1个F508del-CFTR等位基因的囊性纤维化（CF）患者的3期试验显示，ELX/TEZ/IVA对肺功能、体重和肺部恶化（PEx）有显著的短期影响。作者进行了一项为期 12 个月的研究，旨在为葡萄牙 CF 成人患者使用 ELX/TEZ/IVA 进行 CFTR 调节剂治疗的长期有效性和安全性提供更多证据。研究纳入了在临床试验之外接受ELX/TEZ/IVA组合治疗的成年患者。结果 132 名成年 CF 患者被纳入研究，其中 119 人完成了 12 个月的治疗（平均治疗时间为 21.5 个月）。平均年龄为（31.7 ± 11.0）岁，53%的患者为F508del变异基因同源，基线汗液氯化物为（86.7 ± 25.9）毫摩尔/升，治疗前预测FEV1百分比为（77.9 ± 19.7）%。1 年后，FEV1 与基线相比的平均绝对值变化为 +0.46L（95 % CI：0.37, 0.55；p < 0.001）和 +13.9个百分点（95 % CI：11.5, 16.2；p < 0.001）。前列腺增生发作减少了 78 %（p <0.001），因前列腺增生住院治疗减少了 91.4 %（p <0.001）。体重指数（BMI）增加了 1.2 kg/m2 (95 % CI: 0.9, 1.5; p <0.001)。平均汗液氯化物变化为 -44.5 mmol/L (95 % CI: -49.8, -39.2; p <0.001)。未发现汗液氯化物与肺功能之间存在相关性（r = -0.116，p = 0.335）。没有重大的安全问题。结论ELX/TEZ/IVA对葡萄牙成年CF患者的治疗与肺功能的显著改善、PEx和PEx相关住院率的下降以及12个月后BMI的增加有关，并且耐受性良好。这些结果使我们对ELX/TEZ/IVA的临床疗效和耐受性有了更深入的了解。仔细评估ELX/TEZ/IVA疗法的不良反应及其决定因素（主要涉及心理健康）是研究的当务之急。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Elexacaftor/tezacaftor/ivacaftor, a game-changer in cystic fibrosis: The Portuguese experience

Background

Phase 3 trials of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) combination treatment in people with cystic fibrosis (CF) with ≥1 F508del-CFTR allele showed profound short-term effects on lung function, weight, and pulmonary exacerbations (PEx). The authors conducted a 12-month study to add evidence on the real-world long-term effectiveness and safety of CFTR modulator therapy with ELX/TEZ/IVA in Portuguese CF adult population.

Methods

Ambispective, multicentre, observational, real-life study involving all the Portuguese CF Reference Centres. Adult patients on treatment with ELX/TEZ/IVA combination outside clinical trials were included. Demographics, efficacy, and safety variables on the first 12 months of treatment were compared with the pre-treatment year.

Results

132 adult people with CF were included, of which 119 completed 12 months treatment (mean duration of treatment 21.5 months). Mean age was 31.7 ± 11.0 years, 53 % patients were homozygous for the F508del variant, baseline sweat chloride was 86.7 ± 25.9 mmol/L and pre-treatment percent-predicted FEV₁ was 77.9 ± 19.7 %. At 1 year, mean absolute change from baseline in FEV₁ was +0.46L (95 % CI: 0.37, 0.55; p < 0.001) and +13.9 percentage points (95 % CI: 11.5, 16.2; p < 0.001). PEx episodes decreased by 78 % (p < 0.001) and hospitalizations for PEx decreased by 91.4 % (p < 0.001). Body mass index (BMI) increased 1.2 kg/m² (95 % CI: 0.9, 1.5; p < 0.001). Mean sweat chloride variation was −44.5 mmol/L (95 % CI: −49.8, −39.2; p < 0.001). No correlation was found between sweat chloride and lung function (r = −0.116, p = 0.335). There were no major safety concerns. Of note, headache was reported in 7.6 % and neuropsychiatric manifestations occurred in 12.6 % treated patients, being anxiety and depressive disorders the most common.

Conclusions

ELX/TEZ/IVA treatment in Portuguese adults with CF was associated with significant improvement in lung function, a drop in PEx and PEx-related hospitalizations and increase in BMI at 12 months and was well tolerated. These results add knowledge to our understanding of clinical benefits and tolerability of ELX/TEZ/IVA. Careful evaluation of adverse effects of ELX/TEZ/IVA therapy and its determinants, mainly concerning mental health, are a research priority.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

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.