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 ERTexperienced 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 change...
| Autores: | , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | Brasil |
| Recursos: | Universidade Federal do Rio Grande do Sul (UFRGS) |
| Repositorio: | Repositório Institucional da UFRGS |
| Idioma: | inglés |
| OAI Identifier: | oai:www.lume.ufrgs.br:10183/234529 |
| Acesso em linha: | http://hdl.handle.net/10183/234529 |
| Access Level: | acceso abierto |
| Palavra-chave: | Doença de Fabry Fenótipo Eficácia Testes de função renal Resultado do tratamento Classic phenotype Efficacy Fabry disease Chaperone Migalastat Renal function |
| Resumo: | The effect of migalastat on long-term renal outcomes in enzyme replacement therapy (ERT)–naive and ERTexperienced 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 m2 ) and ERT-experienced (n = 42 [24 females]; mean age, 50 years; mean baseline eGFR, 89.2 mL/min/1.73m2 ) 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 (eGFRCKD-EPI) was calculated by both simple linear regression and a random coefficient model. In ERT-naive patients, mean annualized rates of change from baseline in eGFRCKD-EPI were − 1.6 mL/min/1.73 m2 overall and − 1.8 mL/min/1.73 m2 and − 1.4 mL/min/1.73 m2 in male and female patients, respectively, as estimated by simple linear regression. In ERT-experienced patients, mean annualized rates of change from baseline in eGFRCKD-EPI were − 1.6 mL/min/1.73 m2 overall and − 2.6 mL/min/1.73 m2 and − 0.8 mL/min/1.73 m2 in male and female patients, respectively. Mean annualized rate of change in eGFRCKD-EPI 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 m2 . When calculated using the random coefficient model, which adjusted for sex, age, and baseline renal function, the annualized eGFRCKD-EPI change was minimal (mean: − 0.1 and 0.1 mL/min/1.73 m2 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. |
|---|