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Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease.
J Med Genet. 2015 May; 52(5):353-8.JM

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+Show Affiliations

Division of Medical Genetics, University of Versailles-St Quentin en Yvelines, Versailles, France; Assistance Publique-Hopitaux de Paris, Garches, France.Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Centre de Référence des Maladies Héréditaires du Métabolisme, Bron, France.Genzyme, a Sanofi company, Cambridge, Massachusetts, USA.Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK.Genzyme, a Sanofi company, Cambridge, Massachusetts, USA.Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, California, USA.Department of Pediatrics, University of Washington, Seattle, Washington, USA.Independent Medical Consultant (retired from Salford Royal NHS Trust 2011), Manchester, UK.Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, USA.University Research Foundation for Lysosomal Storage Diseases, Coral Springs, Florida, USA.Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25795794

Citation

Germain, Dominique P., et al. "Ten-year Outcome of Enzyme Replacement Therapy With Agalsidase Beta in Patients With Fabry Disease." Journal of Medical Genetics, vol. 52, no. 5, 2015, pp. 353-8.
Germain DP, Charrow J, Desnick RJ, et al. Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. J Med Genet. 2015;52(5):353-8.
Germain, D. P., Charrow, J., Desnick, R. J., Guffon, N., Kempf, J., Lachmann, R. H., Lemay, R., Linthorst, G. E., Packman, S., Scott, C. R., Waldek, S., Warnock, D. G., Weinreb, N. J., & Wilcox, W. R. (2015). Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. Journal of Medical Genetics, 52(5), 353-8. https://doi.org/10.1136/jmedgenet-2014-102797
Germain DP, et al. Ten-year Outcome of Enzyme Replacement Therapy With Agalsidase Beta in Patients With Fabry Disease. J Med Genet. 2015;52(5):353-8. PubMed PMID: 25795794.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. AU - Germain,Dominique P, AU - Charrow,Joel, AU - Desnick,Robert J, AU - Guffon,Nathalie, AU - Kempf,Judy, AU - Lachmann,Robin H, AU - Lemay,Roberta, AU - Linthorst,Gabor E, AU - Packman,Seymour, AU - Scott,C Ronald, AU - Waldek,Stephen, AU - Warnock,David G, AU - Weinreb,Neal J, AU - Wilcox,William R, Y1 - 2015/03/20/ PY - 2014/09/29/received PY - 2015/02/11/accepted PY - 2015/3/22/entrez PY - 2015/3/22/pubmed PY - 2016/1/7/medline KW - Genetics KW - Metabolic disorders SP - 353 EP - 8 JF - Journal of medical genetics JO - J. Med. Genet. VL - 52 IS - 5 N2 - 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. SN - 1468-6244 UR - https://www.unboundmedicine.com/medline/citation/25795794/Ten_year_outcome_of_enzyme_replacement_therapy_with_agalsidase_beta_in_patients_with_Fabry_disease_ L2 - http://jmg.bmj.com/cgi/pmidlookup?view=long&pmid=25795794 DB - PRIME DP - Unbound Medicine ER -