Comparative Efficacy of CFTR Modulators: A Network Meta-analysis.

IF 4.6 2区医学 Q1 RESPIRATORY SYSTEM

Lung Pub Date : 2025-03-18 DOI:10.1007/s00408-025-00802-w

Imran Hasan Iftikhar, Saad T Rao, Rufai Nadama, Ibrahim Janahi, Ahmed S BaHammam

{"title":"Comparative Efficacy of CFTR Modulators: A Network Meta-analysis.","authors":"Imran Hasan Iftikhar, Saad T Rao, Rufai Nadama, Ibrahim Janahi, Ahmed S BaHammam","doi":"10.1007/s00408-025-00802-w","DOIUrl":null,"url":null,"abstract":"Purpose: The objective was to study comparative efficacies of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, vanzacaftor-tezacaftor-deutivacaftor (VTD), elexacaftor-tezacaftor-ivacaftor (ETI), tezacaftor-ivacaftor (Tez-Iva), and lumacaftor-ivacaftor (Lum-Iva) in people with cystic fibrosis (pwCF), aged ≥ 12 years, carrying at least one F508del-CFTR-allele.Methods: Data from randomized controlled or randomized active comparator trials were included in this network meta-analysis which used frequentist approach for comparing the efficacy of drugs and ranking based on P-scores. Outcomes of interest were mean differences in percentage-predicted forced expiratory volume in one second (ppFEV1), CF questionnaire-revised respiratory domain (CFQ-R) scores, sweat chloride (SwCl) levels, and odds ratios (OR) for serious adverse events (SAE).Results: Data from 13 studies were analyzed. Compared to placebo, the effects of VTD and ETI on ppFEV1 were almost quadruple of Tez-Iva and Lum-Iva (VTD: 12.78 [95% confidence intervals: 6.41; 19.15] and ETI: 11.95 [7.40; 16.50]) and almost seven times of Tez-Iva and Lum-Iva for CFQ-R (VTD: 21.23 [- 28.72; 71.18] and ETI: 19.27 [10.56; 27.98]). A statistically significant difference was noted between VTD and ETI in SwCl reduction (mean difference: - 8.59 [- 15.53; - 1.65]). There were no statistically significant ORs for SAEs for any CFTR modulators but VTD, ETI, and Tez-Iva were least associated with SAEs (ORs were 0.15 [0.01; 1.79], 0.49 [0.31; 0.78], and 0.74 [0.50; 1.09], respectively, as compared to placebo). Overall, P-score ranking ranked VTD as first and ETI as second, followed by others.Conclusion: VTD and ETI were more efficacious than Tez-Iva and Lum-Iva in pwCF with at least one F508del-CFTR-allele.","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"49"},"PeriodicalIF":4.6000,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lung","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00408-025-00802-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: The objective was to study comparative efficacies of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, vanzacaftor-tezacaftor-deutivacaftor (VTD), elexacaftor-tezacaftor-ivacaftor (ETI), tezacaftor-ivacaftor (Tez-Iva), and lumacaftor-ivacaftor (Lum-Iva) in people with cystic fibrosis (pwCF), aged ≥ 12 years, carrying at least one F508del-CFTR-allele.

Methods: Data from randomized controlled or randomized active comparator trials were included in this network meta-analysis which used frequentist approach for comparing the efficacy of drugs and ranking based on P-scores. Outcomes of interest were mean differences in percentage-predicted forced expiratory volume in one second (ppFEV₁), CF questionnaire-revised respiratory domain (CFQ-R) scores, sweat chloride (SwCl) levels, and odds ratios (OR) for serious adverse events (SAE).

Results: Data from 13 studies were analyzed. Compared to placebo, the effects of VTD and ETI on ppFEV1 were almost quadruple of Tez-Iva and Lum-Iva (VTD: 12.78 [95% confidence intervals: 6.41; 19.15] and ETI: 11.95 [7.40; 16.50]) and almost seven times of Tez-Iva and Lum-Iva for CFQ-R (VTD: 21.23 [- 28.72; 71.18] and ETI: 19.27 [10.56; 27.98]). A statistically significant difference was noted between VTD and ETI in SwCl reduction (mean difference: - 8.59 [- 15.53; - 1.65]). There were no statistically significant ORs for SAEs for any CFTR modulators but VTD, ETI, and Tez-Iva were least associated with SAEs (ORs were 0.15 [0.01; 1.79], 0.49 [0.31; 0.78], and 0.74 [0.50; 1.09], respectively, as compared to placebo). Overall, P-score ranking ranked VTD as first and ETI as second, followed by others.

Conclusion: VTD and ETI were more efficacious than Tez-Iva and Lum-Iva in pwCF with at least one F508del-CFTR-allele.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Lung 医学-呼吸系统

CiteScore

9.10

自引率

10.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Lung publishes original articles, reviews and editorials on all aspects of the healthy and diseased lungs, of the airways, and of breathing. Epidemiological, clinical, pathophysiological, biochemical, and pharmacological studies fall within the scope of the journal. Case reports, short communications and technical notes can be accepted if they are of particular interest.