Analysis of Renal and Cardiac Outcomes in Male Participants in the Fabry Outcome Survey Starting Agalsidase Alfa Enzyme Replacement Therapy Before and After 18 Years of Age
Parini, Rossella (Istituto di Ricovero e Cura A Carattere Scientifico (IRCCS))
Pintos-Morell, Guillem (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Hennermann, Julia B. (University Medical Center)
Hsu, Ting-Rong (Taipei Veterans General Hospital)
Karabul, Nesrin (University Children's Hospital and Centre for Rare Diseases)
Kalampoki, Vasiliki (Shire (Suïssa))
Gurevich, Andrey (Shire (Suïssa))
Ramaswami, Uma (Royal Free London NHS Foundation Trust)
Universitat Autònoma de Barcelona

Data:	2020
Resum:	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). 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. 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). Renal and/or cardiac disease progression appears attenuated in patients starting ERT in childhood or early adulthood versus patients starting ERT in later adulthood. These findings support early ERT initiation in Fabry disease. ClinicalTrials. gov identifier: NCT03289065.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Agalsidase alfa ; Fabry disease ; Enzyme replacement therapy ; Fabry Outcome Survey ; Estimated glomerular filtration rate ; Left ventricular hypertrophy
Publicat a:	Drug Design, Development and Therapy, Vol. 14 (june 2020) , p. 2149-2158, ISSN 1177-8881

DOI: 10.2147/DDDT.S249433
PMID: 32581513

10 p, 2.0 MB

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