ws06.02胎儿治疗囊性纤维化的药理学。module - cf研究报告

IF 5.4 2区医学 Q1 RESPIRATORY SYSTEM

Journal of Cystic Fibrosis Pub Date : 2025-06-01 DOI:10.1016/j.jcf.2025.03.523

A.-S. Bonnel , T. Bihouee , I. Sermet-Gaudelus , M. Ribault , M. Driessen , S. Benaboud , D. Grévent , N.H. Truong , M. Benhamida , C. Martin , P.-R. Burgel , P. Reix , F. Foissac , Y. Ville , Modul-CF study group

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引用次数: 0

摘要

目的CFTR调节剂（CFTRm）治疗对胎儿肠道并发症、潜在不良胎儿结局和母婴药理学的影响尚缺乏相关数据。方法如果胎儿有CF的遗传诊断，并且携带至少一种对CFTRm应答的变异，则纳入双胎。标准化评估包括CFTRm前磁共振成像（MRI）、重复超声（US）和出生时脐带、母婴血浆中CFTRm药物浓度。结果：我们从正在进行的法国MODUL CF研究中招募了14对男性。一个撤退了。CFTRm疗法(Elexacaftor (ELX)/Tezacaftor (TEZ)/Ivacaftor (IVA) （ETI) n=12, Ivacaftor (IVA) n=1）给予妊娠19至36周的孕妇，中位[IQR]为35 bb0天，作为MI的治疗指征（n=9）或作为胎儿cf相关肠道症状的三级预防（n=4）。一个胎儿在引入ETI后3天肠扩张增加。MRI显示肠闭锁。一组只注射了两剂。另外7例在ETI后14bb0天内观察到MI的消退。胎儿发育和新生儿耐受性良好。6对ELX/TEZ和7对IVA采用脐带与母体血浆浓度比评估胎盘转移。TEZ非常高，中位IQR范围为1.59[1.00-1.85](0.77-3.59)，但IVA和ELX较低，分娩时脐带与产妇比率分别为0.54[0.44-0.55]（0.26-0.57）和0.40[0.36-0.44]（0.23-0.65）。出生时的粪便弹性蛋白酶始终低于200 ng/g，即使在ETI母乳喂养的婴儿中，这3种化合物的血浆浓度残留量和峰值浓度都很低。结论妊娠中期开始使用eti可使心肌梗死在子宫内转移。在ETI开始时，胎儿耐受性需要通过标准化评估来监测。哺乳期给予ETI的益处尚不清楚。

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WS06.02Pharmacology of fetal therapy in cystic fibrosis. Report from the MODUL-CF study

Objectives

Data on the impact of CFTR modulator (CFTRm) therapies on fetal intestinal complications, potential adverse fetal outcomes and maternal foetal pharmacology are lacking.

Methods

Dyads were included if the foetus had a genetic diagnosis of CF and carried at least one variant responsive to CFTRm. Standardized assessment included pre-CFTRm Magnetic Resonance Imaging (MRI), repeated ultrasound (US), and CFTRm drug concentrations in blood cord, maternal and infant plasma at birth.

Results

We enrolled 14 dyads from the ongoing real-world French MODUL CF study. One withdrew. CFTRm therapies (Elexacaftor (ELX)/Tezacaftor (TEZ)/Ivacaftor (IVA) (ETI) n=12, ivacaftor (IVA) n=1) were administered to the pregnant women between 19 and 36 weeks of gestation for a median [IQR] of 35[55] days, either as a curative indication of MI (n=9) or as a tertiary prevention of fetal CF-related intestinal symptoms (n=4). One foetus experienced increased bowel dilatation 3 days after ETI introduction. MRI revealed intestinal atresia. One dyad received only 2 doses. In the other 7 cases, resolution of MI was observed within 14[10] days of ETI. Fetal development and neonatal tolerance were excellent. Placental transfer was assessed by cord-to-maternal plasma concentration ratio in 6 dyads for ELX/TEZ and 7 dyads for IVA. It was very high for TEZ, with a median [IQR] range of 1.59 [1.00–1.85] (0.77-3.59), but low for IVA and ELX, with a respective cord-to-maternal ratio at delivery of 0.54 [0.44–0.55] (0.26–0.57) and 0.40 [0.36–0.44] (0.23-0.65). Fecal elastase at birth was always below 200 ng/g even in the ETI breast-fed infant who had a very low plasma concentration residual and peak concentration of the 3 compounds.

Conclusion

ETI administration from the second trimester of pregnancy enables MI resolution thanks to in utero transfer. Fetal tolerance at ETI initiation needs to be monitored by a standardized assessment. Benefit of ETI administration by lactation is unclear.

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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.