Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease

• Type of Material: Article
• Authors: Dominique P. Germain, University of Versailles—St Quentin en Yvelines; Joel Charrow, Northwestern University; Robert J. Desnick, Icahn School of Medicine at Mount Sinai; Nathalie Guffon, Hopital Femme-Mere-Enfant; Judy Kempf, Genzyme, a Sanofi company; Robin H. Lachmann, National Hospital for Neurology and Neurosurgery; Roberta Lemay, Genzyme, a Sanofi company; Gabor E. Linthorst, University of Amsterdam; Seymour Packman, University of California San Francisco; C. Ronald Scott, University of Washington; Stephen Waldek, Salford Royal NHS Trust 2011; David G. Warnock, University of Alabama Birmingham; Neal J. Weinreb, University Research Foundation for Lysosomal Storage Diseases; William Wilcox, Emory University
• Language: English
• Date: 2015-05-01
• Publisher: BMJ Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © 2015, Published by the BMJ Publishing Group Limited.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/jmedgenet-2014-102797
• Title of Journal or Parent Work: Journal of Medical Genetics
• ISSN: 0022-2593
• Volume: 52
• Issue: 5
• Start Page: 353
• End Page: 358
• Grant/Funding Information: Genzyme, a Sanofi company, funded the clinical trials and the Fabry Registry.
• Keywords: SAFETY; NEPHROPATHY; INVOLVEMENT; Genetics & Heredity; GUIDELINES; REGISTRY; PROGRESSION; Science & Technology; KIDNEY; NATURAL COURSE; Life Sciences & Biomedicine; CLINICAL-MANIFESTATIONS; EFFICACY
• Research Categories: Biology, Genetics

Abstract

Background: Fabry disease results from deficient α-galactosidase A activity and globotriaosylceramide accumulation causing renal insufficiency, strokes, hypertrophic cardiomyopathy and early demise. We assessed the 10-year outcome of recombinant α-galactosidase A therapy. Methods: The outcomes (severe clinical events, renal function, cardiac structure) of 52/58 patients with classic Fabry disease from the phase 3 clinical trial and extension study, and the Fabry Registry were evaluated. Disease progression rates for patients with low renal involvement (LRI, n=32) or high renal involvement (HRI, n=20) at baseline were assessed. Results: 81% of patients (42/52) did not experience any severe clinical event during the treatment interval and 94% (49/52) were alive at the end of the study period. Ten patients reported a total of 16 events. Patients classified as LRI started therapy 13 years younger than HRI (mean 25 years vs 38 years). Mean slopes for estimated glomerular filtration rate for LRI and HRI were -1.89 mL/min/1.73 m²/year and -6.82 mL/ min/1.73 m²/year, respectively. Overall, the mean left ventricular posterior wall thickness and interventricular septum thickness remained unchanged and normal. Patients who initiated treatment at age ≥40 years exhibited significant increase in left ventricular posterior wall thickness and interventricular septum thickness. Mean plasma globotriaosylceramide normalised within 6 months. Conclusions: This 10-year study documents the effectiveness of agalsidase beta (1 mg/kg/2 weeks) in patients with Fabry disease. Most patients remained alive and event-free. Patients who initiated treatment at a younger age and with less kidney involvement benefited the most from therapy. Patients who initiated treatment at older ages and/or had advanced renal disease experienced disease progression.