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Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease.
J Pediatr. 2008 Apr; 152(4):563-70, 570.e1.JPed

Abstract

OBJECTIVE

To evaluate the safety and explore the efficacy of enzyme replacement therapy with agalsidase beta (recombinant human alpha-galactosidase A; Fabrazyme [Genzyme Corporation, Cambridge, MA]) in pediatric patients with Fabry disease, a genetic disorder in which deficient endogenous enzyme causes pathogenic tissue accumulation of globotriaosylceramide (GL-3).

STUDY DESIGN

Fourteen male and 2 female patients, 8 to 16 years old, were treated in this open-label study. A 12-week observation period to collect baseline data preceded the 48-week treatment period when agalsidase beta (1 mg/kg) was infused intravenously every 2 weeks. No primary efficacy end point was specified.

RESULTS

Before treatment, results of skin biopsies from 12 male patients showed moderate or severe GL-3 accumulation in superficial dermal capillary endothelial cells; with treatment, these cells were completely cleared of GL-3 in week-24 biopsies from all 12 male patients and in all available week-48 biopsies. With treatment, reports of gastrointestinal symptoms declined steadily. Patient diaries documented significant reductions in school absences due to sickness. Agalsidase beta was generally well tolerated; most treatment-related adverse events were mild or moderate infusion-associated reactions involving rigors, fever, or rhinitis.

CONCLUSIONS

Agalsidase beta safely and effectively reduced the GL-3 accumulation in dermal endothelium already evident in children with Fabry disease. Early intervention may prevent irreversible end-organ damage from chronic GL-3 deposition.

Authors+Show Affiliations

Royal Manchester Children's Hospital, Manchester, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18346516

Citation

Wraith, J Edmond, et al. "Safety and Efficacy of Enzyme Replacement Therapy With Agalsidase Beta: an International, Open-label Study in Pediatric Patients With Fabry Disease." The Journal of Pediatrics, vol. 152, no. 4, 2008, pp. 563-70, 570.e1.
Wraith JE, Tylki-Szymanska A, Guffon N, et al. Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease. J Pediatr. 2008;152(4):563-70, 570.e1.
Wraith, J. E., Tylki-Szymanska, A., Guffon, N., Lien, Y. H., Tsimaratos, M., Vellodi, A., & Germain, D. P. (2008). Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease. The Journal of Pediatrics, 152(4), 563-70, e1. https://doi.org/10.1016/j.jpeds.2007.09.007
Wraith JE, et al. Safety and Efficacy of Enzyme Replacement Therapy With Agalsidase Beta: an International, Open-label Study in Pediatric Patients With Fabry Disease. J Pediatr. 2008;152(4):563-70, 570.e1. PubMed PMID: 18346516.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease. AU - Wraith,J Edmond, AU - Tylki-Szymanska,Anna, AU - Guffon,Nathalie, AU - Lien,Y Howard, AU - Tsimaratos,Michel, AU - Vellodi,Ashok, AU - Germain,Dominique P, Y1 - 2007/12/03/ PY - 2006/12/28/received PY - 2007/07/19/revised PY - 2007/09/05/accepted PY - 2008/3/19/pubmed PY - 2008/3/26/medline PY - 2008/3/19/entrez SP - 563-70, 570.e1 JF - The Journal of pediatrics JO - J Pediatr VL - 152 IS - 4 N2 - OBJECTIVE: To evaluate the safety and explore the efficacy of enzyme replacement therapy with agalsidase beta (recombinant human alpha-galactosidase A; Fabrazyme [Genzyme Corporation, Cambridge, MA]) in pediatric patients with Fabry disease, a genetic disorder in which deficient endogenous enzyme causes pathogenic tissue accumulation of globotriaosylceramide (GL-3). STUDY DESIGN: Fourteen male and 2 female patients, 8 to 16 years old, were treated in this open-label study. A 12-week observation period to collect baseline data preceded the 48-week treatment period when agalsidase beta (1 mg/kg) was infused intravenously every 2 weeks. No primary efficacy end point was specified. RESULTS: Before treatment, results of skin biopsies from 12 male patients showed moderate or severe GL-3 accumulation in superficial dermal capillary endothelial cells; with treatment, these cells were completely cleared of GL-3 in week-24 biopsies from all 12 male patients and in all available week-48 biopsies. With treatment, reports of gastrointestinal symptoms declined steadily. Patient diaries documented significant reductions in school absences due to sickness. Agalsidase beta was generally well tolerated; most treatment-related adverse events were mild or moderate infusion-associated reactions involving rigors, fever, or rhinitis. CONCLUSIONS: Agalsidase beta safely and effectively reduced the GL-3 accumulation in dermal endothelium already evident in children with Fabry disease. Early intervention may prevent irreversible end-organ damage from chronic GL-3 deposition. SN - 1097-6833 UR - https://www.unboundmedicine.com/medline/citation/18346516/Safety_and_efficacy_of_enzyme_replacement_therapy_with_agalsidase_beta:_an_international_open_label_study_in_pediatric_patients_with_Fabry_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3476(07)00852-9 DB - PRIME DP - Unbound Medicine ER -