期刊
DRUG DESIGN DEVELOPMENT AND THERAPY
卷 14, 期 -, 页码 2149-2158出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S249433
关键词
agalsidase alfa; Fabry disease; enzyme replacement therapy; Fabry Outcome Survey; estimated glomerular filtration rate; left ventricular hypertrophy
资金
- Shire Human Genetic Therapies, Inc., a Takeda company
- Shire International GmbH, a Takeda company
Purpose: To determine the impact of initiating enzyme replacement therapy (ERT) with agalsidase alfa early in the course of Fabry disease, we evaluated renal and cardiac outcomes for <= 10 years after ERT initiation in males from the Fabry Outcome Survey (FOS). Patients and Methods: Male patients from FOS were stratified into three cohorts by age at ERT initiation: <= 18 years (cohort 1), >18 and <= 30 years (cohort 2), and >30 years (cohort 3). Analysis included age at symptom onset, diagnosis, and ERT initiation; ERT duration; FOS-Mainz Severity Score Index (FOS-MSSI); estimated glomerular filtration rate (eGFR); proteinuria level; and left ventricular mass indexed to height (LVMI). Mixed-effect models estimated renal and cardiac outcomes during follow-up between and within cohorts. Findings: The analysis included 560 male patients: 151 (27.0%) in cohort 1, 155 (27.7%) in cohort 2, and 254 (45.4%) in cohort 3. Mean +/- SD duration of ERT for cohorts 1, 2, and 3 was 6.3 +/- 4.3, 8.6 +/- 4.9, and 7.9 +/- 4.9 years, respectively. Mean+SD baseline FOS-MSSI scores increased with age from 9.8 +/- 7.2 in cohort 1 to 24.7 +/- 11.4 in cohort 3. Cohort 3 showed the lowest baseline mean +/- SD value for eGFR (87.1 +/- 29.0 mL/min/1.73m(2)) and highest baseline mean +/- SD values for proteinuria (801.9 +/- 952.6 mg/day) and LVMI (56.7 +/- 16.0 g/m(2)(.7)) among the three cohorts. Evaluation of mean annual rates of change in eGFR, proteinuria, and LVMI revealed no significant differences in any parameter for cohort 1. For cohort 2, proteinuria and LVMI remained stable, whereas eGFR significantly deteriorated annually (-1.12 mL/min/1.73m(2); P<0.001). Cohort 3 demonstrated significant annual deteriorations in eGFR (-2.60 mL/min/1.73m(2); P<0.001), proteinuria (+34.10 mg/day; P<0.001), and LVMI (+0.59 g/m(2.7); P=0.001).
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