Staci Kallish, Antonia Camporeale, Robert J Hopkin, Ana Jovanovic, Peter Nordbeck, Biliana O Veleva-Rotse, Eva Krusinska, Roser Torra
{"title":"米加拉司他治疗女性法布里病的长期疗效。","authors":"Staci Kallish, Antonia Camporeale, Robert J Hopkin, Ana Jovanovic, Peter Nordbeck, Biliana O Veleva-Rotse, Eva Krusinska, Roser Torra","doi":"10.1136/jmg-2024-110596","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Fabry disease is a progressive, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to <i>GLA</i> variants. Females with Fabry disease often experience diagnostic delays and an underappreciated disease burden owing to their variable disease presentation and progression.</p><p><strong>Methods: </strong>We conducted a <i>post hoc</i> 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).</p><p><strong>Results: </strong>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/m<sup>2</sup>/year regardless of LVH or eGFR category at baseline. Mean (SD) eGFR annualised change was -1.1 (2.8) mL/min/1.73 m<sup>2</sup> 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Long-term efficacy of migalastat in females with Fabry disease.\",\"authors\":\"Staci Kallish, Antonia Camporeale, Robert J Hopkin, Ana Jovanovic, Peter Nordbeck, Biliana O Veleva-Rotse, Eva Krusinska, Roser Torra\",\"doi\":\"10.1136/jmg-2024-110596\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Fabry disease is a progressive, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to <i>GLA</i> variants. Females with Fabry disease often experience diagnostic delays and an underappreciated disease burden owing to their variable disease presentation and progression.</p><p><strong>Methods: </strong>We conducted a <i>post hoc</i> 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).</p><p><strong>Results: </strong>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/m<sup>2</sup>/year regardless of LVH or eGFR category at baseline. Mean (SD) eGFR annualised change was -1.1 (2.8) mL/min/1.73 m<sup>2</sup> 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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":16237,\"journal\":{\"name\":\"Journal of Medical Genetics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Medical Genetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/jmg-2024-110596\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jmg-2024-110596","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
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.
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.