Long-term follow-up of renal function in patients treated with migalastat for Fabry disease
Bichet, Daniel G. (Department of Medicine, Hôpital du Sacré-Coeur, University of Montréal, Montreal, Quebec, Canada)
Torra Balcells, Roser (Institut d'Investigació Biomèdica Sant Pau)
Wallace, Eric (Department of Medicine, University of Alabama, Birmingham, AL, USA)
Hughes, Derralynn A (Lysosomal Storage Disorders Unit, Royal Free London NHS Foundation Trust and University College London, London, UK)
Giugliani, Roberto (Instituto Nacional de Genética Médica Populacional (Porto Alegre, Brasil))
Skuban, Nina (Amicus Therapeutics, Inc., Cranbury, NJ, USA)
Krusinska, Eva (Amicus Therapeutics, Inc., Cranbury, NJ, USA)
Feldt-Rasmussen, Ulla (Copenhagen University Hospital Rigshospitalet)
Schiffmann, Raphael (Institute of Metabolic Disease, Baylor Scott & White Research Institute, Dallas, TX, USA)
Nicholls, Kathy (Royal Melbourne Hospital (Melbourne, Austràlia))
Universitat Autònoma de Barcelona

Date:	2021
Abstract:	The effect of migalastat on long-term renal outcomes in enzyme replacement therapy (ERT)-naive and ERT-experienced patients with Fabry disease is not well defined. An integrated posthoc analysis of the phase 3 clinical trials and open-label extension studies was conducted to evaluate long-term changes in renal function in patients with Fabry disease and amenable GLA variants who were treated with migalastat for ≥2 years during these studies. The analysis included ERT-naive (n = 36 [23 females]; mean age 45 years; mean baseline estimated glomerular filtration rate (eGFR), 91. 4 mL/min/mL/1. 73 m 2) and ERT-experienced (n = 42 [24 females]; mean age, 50 years; mean baseline eGFR, 89. 2 mL/min/1. 73m 2) patients with amenable variants who received migalastat 123 mg every other day for ≥2 years. The annualized rate of change from baseline to last observation in estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration equation (eGFR) was calculated by both simple linear regression and a random coefficient model. In ERT-naive patients, mean annualized rates of change from baseline in eGFR were - 1. 6 mL/min/1. 73 m 2 overall and - 1. 8 mL/min/1. 73 m 2 and - 1. 4 mL/min/1. 73 m 2 in male and female patients, respectively, as estimated by simple linear regression. In ERT-experienced patients, mean annualized rates of change from baseline in eGFR were - 1. 6 mL/min/1. 73 m 2 overall and - 2. 6 mL/min/1. 73 m 2 and - 0. 8 mL/min/1. 73 m 2 in male and female patients, respectively. Mean annualized rate of change in eGFR in ERT-naive patients with the classic phenotype (defined by white blood cell alpha galactosidase A [α-Gal A] activity of <3% of normal and multiorgan system involvement) was -1. 7 mL/min/1. 73 m 2. When calculated using the random coefficient model, which adjusted for sex, age, and baseline renal function, the annualized eGFR change was minimal (mean: -0. 1 and 0. 1 mL/min/1. 73 m 2 in ERT-naive and ERT-experienced patients, respectively). In conclusion, patients with Fabry disease and amenable GLA variants receiving long-term migalastat treatment (≤8. 6 years) maintained renal function irrespective of treatment status, sex, or phenotype.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Classic phenotype ; Efficacy ; Fabry disease ; Chaperone ; Migalastat ; Renal function ; α-Gal A, α-galactosidase A ; Gb, globotriaosylceramide ; Egfr, estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration equation ; GLP-HEK, Good Laboratory Practice-validated human embryonic kidney ; LVMi, left ventricular mass index ; Q1, quartile 1 ; Q3, quartile 3 ; RI, renin inhibitor
Published in:	Molecular Genetics and Metabolism Reports, Vol. 28 (august 2021) , ISSN 2214-4269

DOI: 10.1016/j.ymgmr.2021.100786
PMID: 34401344

9 p, 745.9 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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