米加拉司他治疗女性法布里病的长期疗效。

IF 3.7 2区 医学 Q2 GENETICS & HEREDITY
Staci Kallish, Antonia Camporeale, Robert J Hopkin, Ana Jovanovic, Peter Nordbeck, Biliana O Veleva-Rotse, Eva Krusinska, Roser Torra
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引用次数: 0

摘要

背景:Fabry病是一种进行性的x连锁溶酶体疾病,由GLA变异引起的α-半乳糖苷酶a活性降低或缺失引起。女性法布里病往往经历诊断延迟和低估疾病负担,由于其可变的疾病表现和进展。方法:我们对临床研究FACETS (NCT00925301)和ATTRACT (NCT01218659)的所有女性及其开放标签扩展进行了回顾性分析,评估了米加拉司他在心脏和肾脏功能以及fabry相关临床事件(FACEs)方面的基线特征和长期疗效。结果:总体而言,60名女性的中位米加拉司他暴露时间为5.1年。基线时,中位年龄为47岁,70.0%的女性有多器官受累(≥2个器官系统:肾脏、心脏、中枢神经系统、周围神经系统和胃肠道)。在基线时,21.7%的女性患有左心室肥厚(LVH)。在多器官受累和LVH亚组中,肾小球滤过率(eGFR)的中位基线估计在慢性肾病2期。无论基线时LVH或eGFR类别如何,左室质量指数的年化变化率仍低于1g /m2/年。平均(SD) eGFR年化变化为-1.1 (2.8)mL/min/1.73 m2。8名女性报告了10张面孔,其中7人有先前的事件。七面是心脏;其余3例为脑血管(均为短暂性缺血性发作)。肾脏、心脏和脑血管事件的发生率分别为0、24.9和10.7 / 1000患者年。结论:这些数据表明,患有Fabry病的女性有相当大的疾病严重程度和负担,支持米加拉司他治疗女性的长期疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Long-term efficacy of migalastat in females with Fabry disease.

Background: Fabry disease is a progressive, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to GLA variants. Females with Fabry disease often experience diagnostic delays and an underappreciated disease burden owing to their variable disease presentation and progression.

Methods: We conducted a post hoc analysis of all females from the clinical studies FACETS (NCT00925301) and ATTRACT (NCT01218659) and their open-label extensions, assessing baseline characteristics and long-term efficacy of migalastat regarding cardiac and renal function and Fabry-associated clinical events (FACEs).

Results: Overall, 60 females had a median migalastat exposure of 5.1 years. At baseline, the median age was 47 years with multiorgan involvement in 70.0% of females (≥2 organ systems: renal, cardiac, central nervous system, peripheral nervous system and gastrointestinal). At baseline, 21.7% of females had left ventricular hypertrophy (LVH). In multiorgan involvement and LVH subgroups, the median baseline estimated glomerular filtration rate (eGFR) was in chronic kidney disease stage 2. Annualised rate of change in left ventricular mass index remained below 1 g/m2/year regardless of LVH or eGFR category at baseline. Mean (SD) eGFR annualised change was -1.1 (2.8) mL/min/1.73 m2 overall. Ten FACEs were reported in eight females, seven of whom had prior events. Seven FACEs were cardiac; the remaining three were cerebrovascular (all transient ischaemic attacks). The incidence of renal, cardiac and cerebrovascular events was 0, 24.9 and 10.7 events per 1000 patient-years, respectively.

Conclusion: These data show that females with Fabry disease experience considerable disease severity and burden and support the long-term efficacy of migalastat for the treatment of females.

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来源期刊
Journal of Medical Genetics
Journal of Medical Genetics 医学-遗传学
CiteScore
7.60
自引率
2.50%
发文量
92
审稿时长
4-8 weeks
期刊介绍: Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.
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