Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg - PubMed (original) (raw)

Comparative Study

Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg

Anouk C Vedder et al. PLoS One. 2007.

Abstract

Background: Two different enzyme preparations, agalsidase alfa (Replagal(TM), Shire) and beta (Fabrazyme(TM), Genzyme), are registered for treatment of Fabry disease. We compared the efficacy of and tolerability towards the two agalsidase preparations administered at identical protein dose in a randomized controlled open label trial.

Methodology/principal findings: Thirty-four Fabry disease patients were treated with either agalsidase alfa or agalsidase beta at equal dose of 0.2 mg/kg biweekly. Primary endpoint was reduction in left ventricular mass after 12 and 24 months of treatment. Other endpoints included occurrence of treatment failure (defined as progression of cardiac, renal or cerebral disease), glomerular filtration rate, pain, anti-agalsidase antibodies, and globotriaosylceramide levels in plasma and urine. After 12 and 24 months of treatment no reduction in left ventricular mass was seen, which was not different between the two treatment groups. Also, no differences in glomerular filtration rate, pain and decline in globotriaosylceramide levels were found. Antibodies developed only in males (4/8 in the agalsidase alfa group and 6/8 in the agalsidase beta group). Treatment failure within 24 months of therapy was seen in 8/34 patients: 6 male patients (3 in each treatment group) and 2 female patients (both agalsidase alfa). The occurrence of treatment failures did not differ between the two treatment groups; chi(2) = 0.38 p = 0.54.

Conclusion: Our study revealed no difference in reduction of left ventricular mass or other disease parameters after 12 and 24 months of treatment with either agalsidase alfa or beta at a dose of 0.2 mg/kg biweekly. Treatment failure occurred frequently in both groups and seems related to age and severe pre-treatment disease.

Trial registration: International Standard Randomized Clinical Trial ISRCTN45178534 [http://www.controlled-trials.com/ISRCTN45178534\].

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Conflict of interest statement

Competing Interests: Author CH received reimbursement of expenses and small honoraria for lectures on the management of lysosomal storage diseases, including Fabry disease, from Genzyme Corporation, Shire and Actelion. All honoraria are donated to the Gaucher Stichting, a national foundation that supports research in the field of lysosomal storage disorders.

Figures

Figure 1

Figure 1. Study flow chart.

Δ clinical endpoint: change of primary endpoint from improvement of renal function to reduction in left ventricular mass.

Figure 2

Figure 2

A: Kaplan Meier survival analysis of percent patients with no treatment failure in both treatment groups. B: Number of patients with treatment failure displayed per 10 MSSI points. C: Number of patients with treatment failure displayed per age decade.

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