Lenders, Malte, Nordbeck, Peter ORCID: 0000-0002-2560-4068, Kurschat, Christine, Karabul, Nesrin, Kaufeld, Jessica, Hennermann, Julia B., Patten, Monica, Cybulla, Markus, Muentze, Jonas, Ueceyler, Nurcan, Liu, Dan, Das, Anibh M., Sommer, Claudia, Pogoda, Christian, Reiermann, Stefanie, Duning, Thomas, Gaedeke, Jens, Stumpfe, Katharina, Blaschke, Daniela, Brand, Stefan-Martin, Mann, W. Alexander, Kampmann, Christoph, Muschol, Nicole, Canaan-Kuehl, Sima and Brand, Eva (2020). Treatment of Fabry's Disease With Migalastat: Outcome From a Prospective Observational Multicenter Study (FAMOUS). Clin. Pharmacol. Ther., 108 (2). S. 326 - 338. HOBOKEN: WILEY. ISSN 1532-6535

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Abstract

Fabry's disease (FD) is an X-linked lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme alpha-galactosidase A (alpha-Gal A) leading to intracellular accumulation of globotriaosylceramide (Gb3). Patients with amenable mutations can be treated with migalastat, a recently approved oral pharmacologic chaperone to increase endogenous alpha-Gal A activity. We assessed safety along with cardiovascular, renal, and patient-reported outcomes and disease biomarkers in a prospective observational multicenter study after 12 months of migalastat treatment under real-world conditions. Fifty-nine (28 females) patients (34 (57.6%) pretreated with enzyme replacement therapy) with amenable mutations were recruited. Migalastat was generally safe and well tolerated. Females and males presented with a reduction of left ventricular mass index (primary end point) (-7.2 and -13.7 g/m(2), P = 0.0050 and P = 0.0061). FD-specific manifestations and symptoms remained stable (all P > 0.05). Both sexes presented with a reduction of estimated glomerular filtration rate (secondary end point) (-6.9 and -5.0 mL/minute/1.73 m(2); P = 0.0020 and P = 0.0004, respectively), which was most prominent in patients with low blood pressure (P = 0.0271). alpha-Gal A activity increased in male patients by 15% from 29% to 44% of the normal wild-type activity (P = 0.0106) and plasma lyso-Gb3 levels were stable in females and males (P = 0.3490 and P = 0.2009). Reevaluation of mutations with poor biochemical response revealed no marked activity increase in a zero activity background. We conclude that therapy with migalastat was generally safe and resulted in an amelioration of left ventricular mass. In terms of impaired renal function, blood pressure control seems to be an unattended important goal.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Lenders, MalteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nordbeck, PeterUNSPECIFIEDorcid.org/0000-0002-2560-4068UNSPECIFIED
Kurschat, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karabul, NesrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaufeld, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hennermann, Julia B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patten, MonicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cybulla, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muentze, JonasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ueceyler, NurcanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, DanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Das, Anibh M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sommer, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pogoda, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reiermann, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duning, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gaedeke, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stumpfe, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blaschke, DanielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brand, Stefan-MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mann, W. AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kampmann, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muschol, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Canaan-Kuehl, SimaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brand, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-336401
DOI: 10.1002/cpt.1832
Journal or Publication Title: Clin. Pharmacol. Ther.
Volume: 108
Number: 2
Page Range: S. 326 - 338
Date: 2020
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1532-6535
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ENZYME REPLACEMENT THERAPY; PHARMACOLOGICAL CHAPERONE; ALPHA-GALACTOSIDASE; NATURAL-HISTORY; GLOBOTRIAOSYLCERAMIDE; CARDIOMYOPATHY; EVENTS; SAFETY; REDUCTION; MUTATIONSMultiple languages
Pharmacology & PharmacyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33640

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