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Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease.
Genet Med. 2009 Apr; 11(4):256-64.GM

Abstract

PURPOSE

Fabry disease, a genetic deficiency of alpha-galactosidase A, is characterized by pathogenic cellular accumulation of globotriaosylceramide. During clinical trials, recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme, Genzyme Corporation, Cambridge, MA), infused intravenously at 1.0 mg/kg every 2 weeks for 6 months, cleared or reduced globotriaosylceramide in renal, cardiac, and dermal microvascular endothelia and other cells, with results sustained for up to 5 years in most patients evaluated. This study explored whether a lower dose could maintain globotriaosylceramide clearance achieved with 1.0 mg/kg.

METHODS

Cellular globotriaosylceramide levels were assessed histologically in kidney and skin biopsies from 21 adult Fabry males treated for 6 months at 1.0 mg/kg/2 weeks followed by 18 months at 0.3 mg/kg/2 weeks.

RESULTS

In kidney interstitial capillary endothelium, the primary endpoint, globotriaosylceramide clearance was achieved in 100% of patients with 1.0 mg/kg and maintained in 90% with 0.3 mg/kg. In seven other renal cell types and superficial dermal capillary endothelium, globotriaosylceramide reduction or clearance was maintained with 0.3 mg/kg in approximately 70% of patients.

CONCLUSIONS

A lower dose of agalsidase beta may be sufficient in some, but not all, patients with Fabry disease to maintain the cellular globotriaosylceramide clearance achieved with 1.0 mg/kg/2 weeks. Long-term clinical effects of transitioning to the lower dose have not been evaluated.

Authors+Show Affiliations

Clinical Department of Cardiology and Angiology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic. lubanda@mail.czNo 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

19265719

Citation

Lubanda, Jean-Claude, et al. "Evaluation of a Low Dose, After a Standard Therapeutic Dose, of Agalsidase Beta During Enzyme Replacement Therapy in Patients With Fabry Disease." Genetics in Medicine : Official Journal of the American College of Medical Genetics, vol. 11, no. 4, 2009, pp. 256-64.
Lubanda JC, Anijalg E, Bzdúch V, et al. Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease. Genet Med. 2009;11(4):256-64.
Lubanda, J. C., Anijalg, E., Bzdúch, V., Thurberg, B. L., Bénichou, B., & Tylki-Szymanska, A. (2009). Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease. Genetics in Medicine : Official Journal of the American College of Medical Genetics, 11(4), 256-64. https://doi.org/10.1097/GIM.0b013e3181981d82
Lubanda JC, et al. Evaluation of a Low Dose, After a Standard Therapeutic Dose, of Agalsidase Beta During Enzyme Replacement Therapy in Patients With Fabry Disease. Genet Med. 2009;11(4):256-64. PubMed PMID: 19265719.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease. AU - Lubanda,Jean-Claude, AU - Anijalg,Ene, AU - Bzdúch,Vladimír, AU - Thurberg,Beth L, AU - Bénichou,Bernard, AU - Tylki-Szymanska,Anna, PY - 2009/3/7/entrez PY - 2009/3/7/pubmed PY - 2009/9/26/medline SP - 256 EP - 64 JF - Genetics in medicine : official journal of the American College of Medical Genetics JO - Genet Med VL - 11 IS - 4 N2 - PURPOSE: Fabry disease, a genetic deficiency of alpha-galactosidase A, is characterized by pathogenic cellular accumulation of globotriaosylceramide. During clinical trials, recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme, Genzyme Corporation, Cambridge, MA), infused intravenously at 1.0 mg/kg every 2 weeks for 6 months, cleared or reduced globotriaosylceramide in renal, cardiac, and dermal microvascular endothelia and other cells, with results sustained for up to 5 years in most patients evaluated. This study explored whether a lower dose could maintain globotriaosylceramide clearance achieved with 1.0 mg/kg. METHODS: Cellular globotriaosylceramide levels were assessed histologically in kidney and skin biopsies from 21 adult Fabry males treated for 6 months at 1.0 mg/kg/2 weeks followed by 18 months at 0.3 mg/kg/2 weeks. RESULTS: In kidney interstitial capillary endothelium, the primary endpoint, globotriaosylceramide clearance was achieved in 100% of patients with 1.0 mg/kg and maintained in 90% with 0.3 mg/kg. In seven other renal cell types and superficial dermal capillary endothelium, globotriaosylceramide reduction or clearance was maintained with 0.3 mg/kg in approximately 70% of patients. CONCLUSIONS: A lower dose of agalsidase beta may be sufficient in some, but not all, patients with Fabry disease to maintain the cellular globotriaosylceramide clearance achieved with 1.0 mg/kg/2 weeks. Long-term clinical effects of transitioning to the lower dose have not been evaluated. SN - 1530-0366 UR - https://www.unboundmedicine.com/medline/citation/19265719/Evaluation_of_a_low_dose_after_a_standard_therapeutic_dose_of_agalsidase_beta_during_enzyme_replacement_therapy_in_patients_with_Fabry_disease_ L2 - https://doi.org/10.1097/GIM.0b013e3181981d82 DB - PRIME DP - Unbound Medicine ER -