Safety and Efficacy of Enzyme Replacement Therapy with Agalsidase Beta: An International, Open-label Study in Pediatric Patients with Fabry Disease - 07/03/14
Résumé |
Objective |
To evaluate the safety and explore the efficacy of enzyme replacement therapy with agalsidase beta (recombinant human ⍺-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.
Le texte complet de cet article est disponible en PDF.Abbreviations : AE, ⍺Gal, BMI, ECG, ELISA, ERT, IAR, IV, GFR, GL-3, IgE, IgG, OMIM, r-h⍺Gal, SAE
Plan
Sponsored by Genzyme Corporation. |
|
This trial has been registered at clinicaltrials.gov. The study ID# is NCT00074958. |
|
Conflict-of-Interest Disclosures: Dr Wraith has received honoraria and consulting fees from Genzyme; Dr Tylki-Szymanska has received honoraria and consulting fees from Genzyme; Dr Guffon received a research grant from Genzyme; Dr Lien has received research grants from Genzyme and Shire; Dr Tsimaratos has received honoraria from Genzyme and Shire; Dr Vellodi has received honoraria from Genzyme; and Dr Germain has receieved a research grant and consulting fees from Genzyme. |
Vol 152 - N° 4
P. 563 - avril 2008 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?