在南非（SA） CF患者中，使用标准对照克拉霉素增强gETI，节省调制剂策略降低成本的实际结果。

IF 5.4 2区医学 Q1 RESPIRATORY SYSTEM

Journal of Cystic Fibrosis Pub Date : 2025-03-01 DOI:10.1016/j.jcf.2025.02.002

Marco Zampoli , Janine Verstraete , Cathy Baird , Tony Biebuyck , Greg Calligaro , Marina Coetzee , Carla Els , Marlize Frauendorf , Paul Gebers , Brenda Morrow , Dave Richards , Hanri Truter , Andrew Hill

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引用次数: 0

摘要

目的：在资源有限的国家，高效调节疗法（HEMT）的可及性受到高昂的成本和限制性专利的限制。我们报告了南非（SA）降低成本策略的临床结果，在符合HEMT条件的CF （pwCF）患者中，克拉霉素（gETI/c）增强了通用eleexacaftor /tezacaftor/ivacaftor （gETI）的药代动力学。方法：于2021年12月至2024年5月进行多中心观察研究。采用方差分析（ANOVA）和线性混合效应分析来描述和比较不同gETI剂量类别(a)标准剂量、完全剂量或b)调节剂保留剂量（gETI/c在推荐剂量的25- 50%，每周2 / 3次）18个月随访期间汗氯（SC）、FEV1pp、BMI （m/kg2）和不良事件（AE）的变化。结果：70/413例（17%）符合pwCF条件[中位年龄27岁（范围6-52岁）；68例(97%)≥1个拷贝F508del患者接受了标准剂量（n = 38）或保留调节剂剂量（n = 32）的gETI治疗；29名患者在整个研究期间改变了给药方案。治疗1个月后SC总平均（SD）降低为-52.9 (16.9)mmol/L (p < 0.001)，剂量组间无差异（p = 0.2）。总平均（SD） FEV1pp和BMI在1个月分别增加14.9 （95% CI 11.49-18.40）和0.84 （95% CI 0.16-1.49）。FEV1pp和BMI的改善在整个随访过程中持续，没有证据表明不同给药组之间存在差异。没有严重的ae报告。结论：我们使用gETI的经验与使用原始产品的真实报告相似。使用cyp3a抑制剂促进ETI是一种安全有效的策略，可以在HEMT治疗受限的环境中增加ETI治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Real-world outcomes of generic elexacaftor/tezacaftor/ivacaftor (gETI) in South Africans (SA) with CF using standard versus clarithromycin-boosted gETI, modulator-sparing strategies to reduce cost

Objective

Access to highly effective modulator therapies (HEMT) in resource-limited countries is limited by prohibitive cost and restrictive patents. We report the clinical outcomes of a cost-reduction strategy in South Africa (SA), where generic elexacaftor/tezacaftor/ivacaftor (gETI) was pharmacokinetically enhanced with clarithromycin (gETI/c) for people with CF (pwCF) eligible for HEMT.

Methods

A multi-center observational study from December 2021 to May 2024. Analysis of variance (ANOVA) and linear mixed effects analyses were conducted to describe and compare change in sweat chloride (SC), FEV1pp, BMI (m/kg²) and adverse events (AE) over 18-months follow-up for different gETI dose categories: a) standard, full or b) modulator sparing dose (gETI/c at 25–50 % recommended dose, twice/thrice weekly).

Results

70/413 (17 %) eligible pwCF [median age 27 years (range 6–52); 68 (97 %) with ≥ one copy F508del] received gETI with standard (n = 38) or modulator-sparing doses (n = 32); 29 changed dosing regimens across the study period. The overall mean (SD) reduction in SC after 1-month of treatment was -52.9 (16.9) mmol/L (p < 0.001), with no evidence of difference between dose groups (p = 0.2). Overall mean (SD) FEV1pp and BMI increased at 1-month by 14.9 (95 % CI 11.49–18.40) and 0.84 (95 % CI 0.16–1.49), respectively. Improvements in FEV1pp and BMI were sustained throughout follow-up, with no evidence of difference between dosing groups. No serious AEs were reported.

Conclusion

Our experience with gETI is similar to real-world reports using the originator product. Boosting ETI with CYP3A-inhibitors is a safe and effective strategy to increase access to ETI in settings where access to HEMT is restricted.

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来源期刊

Journal of Cystic Fibrosis 医学-呼吸系统

CiteScore

10.10

自引率

13.50%

发文量

1361

审稿时长

50 days

期刊介绍： The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.