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Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease.
Nephrol Dial Transplant. 2007 Jul; 22(7):1920-5.ND

Abstract

BACKGROUND

Fabry disease (FD) is caused by an X-linked deficiency in the activity of alpha-galactosidase A and the resultant accumulation of globotriaosylceramide (Gb3) in multiple tissues. Nearly all classically affected males with FD experience kidney dysfunction, with progression to end-stage renal disease (ESRD) in the third decade of life or shortly thereafter.

METHODS

Twenty-two FD patients (20 men and 2 women) receiving dialysis or who had a history of kidney transplantation were treated with agalsidase alfa in an open label setting using the same dosing regimen given to patients without ESRD (0.2 mg/kg every other week). Pharmacokinetics (PK) were determined during and following the initial dose, and safety was evaluated during therapy. Change in plasma Gb3 level was used as a surrogate marker of enzyme activity in vivo.

RESULTS

A typical biphasic plasma elimination profile was seen in both dialysis and transplant patients, similar to that observed in 18 non-ESRD FD patients. Calculated PK parameters were similar to the three patient groups. In the male patients, plasma Gb3 level declined by 43% after 6 months (P<0.001). Infusion reactions were experienced by 8 of 21 (38%) patients, but did not result in any infusions being stopped prematurely. Anti-agalsidase alfa IgG antibodies were detected in 15.8% of males and 0% female patients. No anti-agalsidase alfa IgE antibodies were detected.

CONCLUSIONS

The same dosing regimen of agalsidase alfa may be safely administered to FD patients with ESRD as given to those without ESRD.

Authors+Show Affiliations

Department of Neurology, New York University School of Medicine, 403 East 34th Street, New York, NY 10016, and St. Louis Children's Hospital, MO, USA. gregory.pastores@med.nyu.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study

Language

eng

PubMed ID

17395657

Citation

Pastores, Gregory M., et al. "Safety and Pharmacokinetics of Agalsidase Alfa in Patients With Fabry Disease and End-stage Renal Disease." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 22, no. 7, 2007, pp. 1920-5.
Pastores GM, Boyd E, Crandall K, et al. Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease. Nephrol Dial Transplant. 2007;22(7):1920-5.
Pastores, G. M., Boyd, E., Crandall, K., Whelan, A., Piersall, L., & Barnett, N. (2007). Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 22(7), 1920-5.
Pastores GM, et al. Safety and Pharmacokinetics of Agalsidase Alfa in Patients With Fabry Disease and End-stage Renal Disease. Nephrol Dial Transplant. 2007;22(7):1920-5. PubMed PMID: 17395657.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease. AU - Pastores,Gregory M, AU - Boyd,Ellen, AU - Crandall,Kerry, AU - Whelan,Alison, AU - Piersall,Linda, AU - Barnett,Natalie, Y1 - 2007/03/29/ PY - 2007/3/31/pubmed PY - 2007/10/17/medline PY - 2007/3/31/entrez SP - 1920 EP - 5 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol Dial Transplant VL - 22 IS - 7 N2 - BACKGROUND: Fabry disease (FD) is caused by an X-linked deficiency in the activity of alpha-galactosidase A and the resultant accumulation of globotriaosylceramide (Gb3) in multiple tissues. Nearly all classically affected males with FD experience kidney dysfunction, with progression to end-stage renal disease (ESRD) in the third decade of life or shortly thereafter. METHODS: Twenty-two FD patients (20 men and 2 women) receiving dialysis or who had a history of kidney transplantation were treated with agalsidase alfa in an open label setting using the same dosing regimen given to patients without ESRD (0.2 mg/kg every other week). Pharmacokinetics (PK) were determined during and following the initial dose, and safety was evaluated during therapy. Change in plasma Gb3 level was used as a surrogate marker of enzyme activity in vivo. RESULTS: A typical biphasic plasma elimination profile was seen in both dialysis and transplant patients, similar to that observed in 18 non-ESRD FD patients. Calculated PK parameters were similar to the three patient groups. In the male patients, plasma Gb3 level declined by 43% after 6 months (P<0.001). Infusion reactions were experienced by 8 of 21 (38%) patients, but did not result in any infusions being stopped prematurely. Anti-agalsidase alfa IgG antibodies were detected in 15.8% of males and 0% female patients. No anti-agalsidase alfa IgE antibodies were detected. CONCLUSIONS: The same dosing regimen of agalsidase alfa may be safely administered to FD patients with ESRD as given to those without ESRD. SN - 0931-0509 UR - https://www.unboundmedicine.com/medline/citation/17395657/Safety_and_pharmacokinetics_of_agalsidase_alfa_in_patients_with_Fabry_disease_and_end_stage_renal_disease_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfm096 DB - PRIME DP - Unbound Medicine ER -