Long-term follow-up of renal function in patients treated with migalastat for Fabry disease
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 chang...
| Autores: | , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:248892 |
| Acceso en línea: | https://ddd.uab.cat/record/248892 https://dx.doi.org/urn:doi:10.1016/j.ymgmr.2021.100786 |
| Access Level: | acceso abierto |
| Palabra clave: | 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 |
| Sumario: | 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. |
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