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

Authors Ramaswami U, Beck M, Hughes D, Kampmann C, Botha J, Pintos-Morell G, West ML, Niu DM, Nicholls K, Giugliani R

Received 7 March 2019

Accepted for publication 27 September 2019

Published 25 October 2019 Volume 2019:13 Pages 3705—3715


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Sukesh Voruganti

Uma Ramaswami,1 Michael Beck,2 Derralynn Hughes,1 Christoph Kampmann,2 Jaco Botha,3 Guillem Pintos-Morell,4 Michael L West,5 Dau-Ming Niu,6 Kathy Nicholls,7,8 Roberto Giugliani9
On behalf of the FOS Study Group 

1Royal Free London NHS Foundation Trust, Lysosomal Disorders Unit, Institute of Immunity and Transplantation, London, UK; 2Centre for Paediatric and Adolescent Medicine, University Medical Centre, University of Mainz, Mainz, Germany; 3Department of Biostatistics and Programming, Takeda, Zug, Switzerland; 4Centre for Rare Diseases, University Hospital Vall d’Hebron, Barcelona, CIBERER-GCV08_IGTP Research Institute and Teaching Unit Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain; 5Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; 6Department of Paediatrics, Taipei Veterans General Hospital, Taipei, Taiwan; 7Department of Nephrology, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia; 8Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia; 9Medical Genetics Service HCPA, Department of Genetics, UFRGS, and INAGEMP, Porto Alegre, Brazil

Correspondence: Uma Ramaswami
Lysosomal Disorders Unit, Institute of Immunity and Transplantation, 2nd Floor, Royal Free Hospital, Pond Street, London NW3 2QG, UK
Tel +44 207 794 0500 Ext 22492
Fax +44 207 317 7665

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 ( 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.

Keywords: agalsidase alfa, enzyme replacement therapy, Fabry disease, cardio-renal outcomes

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