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. 2012:3:33-43.
doi: 10.1007/8904_2011_44. Epub 2011 Sep 15.

Effect of reduced agalsidase Beta dosage in fabry patients: the Australian experience

Joanna Ghali  1 , Kathy Nicholls, Charles Denaro, David Sillence, Ian Chapman, Jack Goldblatt, Mark Thomas, Janice Fletcher; Australian State Fabry Disease Treatment Centres
Affiliations

Effect of reduced agalsidase Beta dosage in fabry patients: the Australian experience

Joanna Ghali et al. JIMD Rep. 2012.

Abstract

Background: In Australia, enzyme replacement therapy (ERT) for Fabry Disease (FD), both Agalsidase alfa (Replagal, Shire HGT) and beta (Fabrazyme, Genzyme), is funded and monitored through a specific government program. Agalsidase beta supply has been rationed by Genzyme since 2009 due to manufacturing issues. Consequently, the Australian Fabry Disease Advisory Committee has treated patients on Agalsidase beta at 50% of their usual dose from mid-2009, with a further reduction to 30% for some patients from late 2009.

Aim: To determine the clinical effect of Agalsidase beta dose reduction in the Australian FD patient cohort.

Methods: A questionnaire assessing FD symptoms was administered to 40 patients on long-term ERT. Clinical data from The Fabry Registry for patients receiving Agalsidase alfa or beta, for at least 2 years prior to the time of enforced Agalsidase beta dose reduction, were reviewed. Disease burden and quality of life (QOL) were graded using the Disease Severity Scoring System, Mainz Severity Score Index, Brief Pain Inventory and Short Form 36 Health Survey at 2 years before dose reduction, at the time of dose reduction and at the most recent clinical review following dose reduction.

Results: Disease severity and QOL scores did not change between the ERT groups. Males on Agalsidase beta reported lower energy levels after dose reduction, while no change was reported by females on either product or by males on a stable dose of Agalsidase alfa.

Conclusion: This study suggests that energy levels in male patients worsen after dose reduction of Agalsidase beta.

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Figures

Fig. 1
Fig. 1
Energy level for patients receiving enzyme replacement therapy. Anova p = 0.03. Note: One patient in the Agalsidase beta group has been excluded from this analysis, as this patient was unable to recall their energy levels 12 months earlier
Fig. 2
Fig. 2
Energy level in male Agalsidase beta patients (n = 22). Wilcoxon matched-pairs signed rank test p = 0.007
Fig. 3
Fig. 3
Energy level in female Agalsidase beta patients (n = 5). Wilcoxon matched-pairs signed rank test. p = 0.25. Note: 2 patients recorded the same energy level scores pre- and postreduction
Fig. 4
Fig. 4
Disease Severity Scoring System (DS3) total scores over time for patients receiving enzyme replacement therapy. ANOVA p = 0.8
Fig. 5
Fig. 5
Mainz Severity Score Index (MSSI) total scores over time for patients receiving enzyme replacement therapy. ANOVA p = 0.92
See this image and copyright information in PMC

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