Long-term follow-up of renal function in patients treated with migalastat for Fabry disease

Mol Genet Metab Rep 2021 Aug 4;28:100786. doi: 10.1016/j.ymgmr.2021.100786.

PMID: 34401344

Daniel G Bichet, Roser Torra, Eric Wallace

Highlights: Regardless of treatment status, sex or phenotype, individuals with Fabry disease and amenable GLA variants who received long-term migalastat therapy (≤8.6 years) preserved renal function.

Abstract

Objective: The effect of migalastat on long-term renal outcomes in Fabry disease patients who are ERT-naive and ERT-experienced is not well understood. Long-term changes in renal function in individuals with Fabry disease and amenable GLA variants who were treated with migalastat for ≥2 years during these investigations were evaluated using an integrated posthoc analysis of phase 3 clinical trials and open-label extension studies.

Methods: Patients with amenable variants who received migalastat 123 mg every other day for ≥2 years were categorized as 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) or ERT-experienced (n = 42 [24 females]; mean age 50 years; mean baseline eGFR, 89.2 mL/min/1.73m2). Simple linear regression and a random coefficient model were used to determine the annualized rate of change in estimated glomerular filtration rate from baseline to final observation using the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI).

Results: According to simple linear regression, the mean annualized rates of change from baseline in eGFRCKD-EPI in ERT-naive patients 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. The mean annualized rates of change from baseline in eGFRCKD-EPI in ERT-experienced patients 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. In ERT-naive individuals with the classic phenotype (defined by white blood cell alpha galactosidase A [-Gal A] activity of 3% of normal and multiorgan system involvement), the mean annualized rate of change in eGFRCKD-EPI was -1.7 mL/min/1.73 m2. The annualized eGFRCKD-EPI change was minimal when computed using the random coefficient model, which accounted for sex, age, and baseline renal function (mean: -0.1 and 0.1 mL/min/1.73 m2 in ERT-naive and ERT-experienced patients, respectively).

Conclusion: In conclusion, regardless of treatment status, sex, or phenotype, individuals with Fabry disease and amenable GLA variants who received long-term migalastat therapy (≤8.6 years) preserved renal function.

Keywords: Fabry, Chaperone, GLP-HEK, Gb3, globotriaosylceramide, Migalastat, renin inhibitör, Renal function, eGFRCKD-EPI, α-galactosidase A