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.
Competing interests: None declared.
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Acknowledgements
We thank our Fabry disease coordinators and nurse specialists at all Australian treatment centers for their commitment to retrieving data, in maintaining The Fabry Registry and in assisting with this study.
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Communicated by: Frits Wijburg.
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Synopsis
Australian male Fabry disease patients receiving long-term enzyme replacement therapy (ERT) with Agalsidase beta report reduced energy levels (without a change in disease severity or other quality of life measures) following a 50% reduction in Agalsidase beta dose, as a consequence of the global shortage of this product.
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All authors have received travel support from Genzyme and/or Shire HGT. Dr Nicholls has received research support from Genzyme and Shire HGT. Dr Fletcher and Prof Sillence have received speaker honoraria from Genzyme. Dr Denaro and Prof Sillence have received coordinator support from Genzyme. Genzyme supports Registry data entry for all centers.
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This paper has been produced with the cooperation of the Australian Government Department of Health and Ageing, which funds and administers the Life Saving Drugs Program (LSDP). The analysis which forms the basis of this paper was conducted by the authors without the use or disclosure of personal information of any patient of the LSDP. Any views expressed or conclusions drawn in the paper are entirely those of the authors and do not reflect any views of the Department or the Australian Government.
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Ghali, J. et al. (2011). Effect of Reduced Agalsidase Beta Dosage in Fabry Patients: The Australian Experience. In: JIMD Reports - Case and Research Reports, 2011/3. JIMD Reports, vol 3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_44
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DOI: https://doi.org/10.1007/8904_2011_44
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