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Original article
Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease
  1. Dominique P Germain1,
  2. Joel Charrow2,
  3. Robert J Desnick3,
  4. Nathalie Guffon4,
  5. Judy Kempf5,
  6. Robin H Lachmann6,
  7. Roberta Lemay5,
  8. Gabor E Linthorst7,
  9. Seymour Packman8,
  10. C Ronald Scott9,
  11. Stephen Waldek10,
  12. David G Warnock11,
  13. Neal J Weinreb12,
  14. William R Wilcox13
  1. 1Division of Medical Genetics, University of Versailles—St Quentin en Yvelines, Versailles, France; Assistance Publique–Hopitaux de Paris, Garches, France
  2. 2Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
  3. 3Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
  4. 4Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Centre de Référence des Maladies Héréditaires du Métabolisme, Bron, France
  5. 5Genzyme, a Sanofi company, Cambridge, Massachusetts, USA
  6. 6Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK
  7. 7Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands
  8. 8Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, California, USA
  9. 9Department of Pediatrics, University of Washington, Seattle, Washington, USA
  10. 10Independent Medical Consultant (retired from Salford Royal NHS Trust 2011), Manchester, UK
  11. 11Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  12. 12University Research Foundation for Lysosomal Storage Diseases, Coral Springs, Florida, USA
  13. 13Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA
  1. Correspondence to Professor Dominique P Germain, Division of Medical Genetics, University of Versailles—St Quentin en Yvelines, Hopital Raymond Poincare (AP-HP), 92380 Garches, France; dominique.germain{at}rpc.aphp.fr

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.

  • Genetics
  • Metabolic disorders

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