title: Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease.
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 m(2)/year and -6.82 mL/min/1.73 m(2)/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.
authors: Division of Medical Genetics, University of Versailles-St Quentin en Yvelines, Versailles, France; Assistance Publique-Hopitaux de Paris, Garches, France.
authors: Dominique P
authors: DP
authors: Germain
authors: Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Joel
authors: J
authors: Charrow
authors: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Robert J
authors: RJ
authors: Desnick
authors: Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Centre de Référence des Maladies Héréditaires du Métabolisme, Bron, France.
authors: Nathalie
authors: N
authors: Guffon
authors: Genzyme, a Sanofi company, Cambridge, Massachusetts, USA.
authors: Judy
authors: J
authors: Kempf
authors: Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK.
authors: Robin H
authors: RH
authors: Lachmann
authors: Genzyme, a Sanofi company, Cambridge, Massachusetts, USA.
authors: Roberta
authors: R
authors: Lemay
authors: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
authors: Gabor E
authors: GE
authors: Linthorst
authors: Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, California, USA.
authors: Seymour
authors: S
authors: Packman
authors: Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors: C Ronald
authors: CR
authors: Scott
authors: Independent Medical Consultant (retired from Salford Royal NHS Trust 2011), Manchester, UK.
authors: Stephen
authors: S
authors: Waldek
authors: Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: David G
authors: DG
authors: Warnock
authors: University Research Foundation for Lysosomal Storage Diseases, Coral Springs, Florida, USA.
authors: Neal J
authors: NJ
authors: Weinreb
authors: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
authors: William R
authors: WR
authors: Wilcox
mesh_terms: D000293:Adolescent; D000328:Adult; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007527:Isoenzymes / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult; D000519:alpha-Galactosidase / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D011994:Recombinant Proteins; D000519:alpha-Galactosidase; C459420:agalsidase beta
keywords: Genetics; Metabolic disorders