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

IF 3.9 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

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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.

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CFTR调制剂的比较疗效：一个网络元分析。

目的：目的是研究囊性纤维化跨膜传导调节剂（CFTR）、vanzacator - tezacator - deutivacator （VTD）、elexacator - tezacator -ivacaftor （ETI）、tezacator -ivacaftor （Tez-Iva）和lumacator -ivacaftor （um- iva）在年龄≥12岁、携带至少一个f508dl -CFTR等位基因的囊性纤维化（pwCF）患者中的比较疗效。方法：本网络荟萃分析采用频率分析方法比较药物的疗效，并根据p评分进行排序。关注的结果是一秒内强迫呼气量百分比预测（ppFEV1）、CF问卷修订呼吸域（CFQ-R）评分、汗液氯化物（SwCl）水平和严重不良事件（SAE）的优势比（OR）的平均差异。结果：分析了13项研究的数据。与安慰剂相比，VTD和ETI对ppFEV1的影响几乎是Tez-Iva和Lum-Iva的四倍(VTD: 12.78[95%置信区间：6.41；19.15] ETI: 11.95 [7.40；16.50])，几乎是CFQ-R的Tez-Iva和Lum-Iva的7倍(VTD: 21.23 [- 28.72；71.18] ETI: 19.27 [10.56；27.98])。VTD和ETI在SwCl减少方面的差异有统计学意义(平均差异：- 8.59 [- 15.53；- 1.65])。任何CFTR调节剂与SAEs的or值均无统计学意义，但VTD、ETI和Tez-Iva与SAEs的相关性最小(or值为0.15 [0.01]；1.79], 0.49 [0.31；0.78], 0.74 [0.50；1.09]，分别与安慰剂相比)。总体而言，P-score排名中VTD排名第一，ETI排名第二，其他公司紧随其后。结论：VTD和ETI治疗至少有一个f508del - cftr等位基因的pwCF疗效优于Tez-Iva和Lum-Iva。

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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.