Cardio- Renal Outcomes With Long- Term Agalsidase Alfa Enzyme Replacement Therapy: A 10- Year Fabry Outcome Survey (FOS) Analysis

Abstract

Agalsidasa alfa; Teràpia de reemplaçament enzimàtic; Malaltia de Fabry

Agalsidasa alfa; Terapia de reemplazo de enzimas; Enfermedad de Fabry

Agalsidase alfa; Enzyme replacement therapy; Fabry disease

Purpose: Following the publication of 5-year agalsidase alfa enzyme replacement therapy (ERT) outcomes data from the Fabry Outcome Survey (FOS), 10-year data were analyzed. Patients and methods: FOS (ClinicalTrials.gov identifier: NCT03289065) data (April 2001 to August 2018) were retrospectively analyzed. Estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) were analyzed after treatment start (baseline) for patients with ≥3 measurements, including baseline and year 10. Results: Median (range) age (years) of the evaluable treated renal cohort at treatment start was 48.8 (17.9–67.3) for females (n=62), 34.4 (18.0–66.8) for males (n=90). With eGFR ≥60 mL/min/1.73 m2 at baseline, mean (95% CI) rate of eGFR change (eGFR/year) over 10 years was relatively stable in females (n=52; −0.55 [−1.12, +0.01]) and slightly declined in males (n=79; −1.99 [−2.45, −1.54]). With impaired kidney function (eGFR <60 mL/min/1.73 m2) at baseline, mean (95% CI) eGFR/year was stable in females (n=10; −0.14 [−1.43, +1.15]) and slightly declined in males (n=11; −2.79 [−4.01, −1.56]) over 10 years. Median (range) age (years) of the evaluable treated cardiac cohort at treatment start was 46.7 (3.7–67.3) for females (n=34), 28.2 (4.0–54.2) for males (n=35). With left ventricular hypertrophy (LVH; LVMI >48 g/m2.7 in females, >50 g/m2.7 in males) at baseline, mean (95% CI) LVMI/year slightly increased over 10 years in females (n=18; +1.51 [+0.91, +2.12]) and males (n=14; +0.87 (+0.19, +1.55). Without LVH at baseline, mean (95% CI) LVMI/year was stable in females (n=16; +0.52 [−0.13, +1.17]) and males (n=21; +0.57 [+0.02, +1.13]) over 10 years. Conclusion: Agalsidase alfa-treated patients with 10-year FOS data and preserved kidney function and/or normal LVMI at baseline remained largely stable; those with decreased kidney function or LVH at baseline experienced modest declines in renal function and/or increases in LVMI.

The Fabry Outcome Survey is sponsored by Shire Human Genetic Therapies, Inc., a member of the Takeda group of companies. Shire International GmbH, a member of the Takeda group of companies, provided funding to Excel Medical Affairs for support in writing and editing this manuscript and participated in data collection and analysis.