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A prospective 10-year study of individualized, intensified enzyme replacement therapy in advanced Fabry disease

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Objectives

To test the hypothesis that more frequent enzyme replacement therapy (ERT) slows the decline in kidney function in adult patients with Fabry disease.

Methods

A single center open label 10-year prospective clinical trial of 12 patients with advanced Fabry disease who, after having experienced an ongoing decline in renal function after 2-4 years of receiving ERT at the approved dose of 0.2 mg/kg agalsidase alfa every other week (EOW), were switched to weekly (EW) ERT at the same dose. We used linear regression to fit each individual patient’s longitudinal estimated glomerular filtration rate (eGFR) record in order to compare the deterioration rates between EOW and EW ERT.

Results

For the entire group, mean slope on agalsidase alfa every 2 weeks was -7.92 ± 2.88 ml/min/1.73 m2/year and 3.84 ± 4.08 ml/min/1.73 m2/year on weekly enzyme infusions (p = 0.01, two-tailed paired t test). Three patients (25 %) completed the entire study with relatively preserved renal function while 50 % of patients reached end-stage renal disease (ESRD) during the 10 years of this study. The estimated average delay to ESRD was 13.8 years [n = 11; 95 % CI 0.66, 27]. One patient had a positive eGFR slope on weekly infusions while the patient with the highest antibody titer had a steeper slope after switching. Mean globotriaosylceramide concentrations in urine and plasma as well as urine protein excretion remained unchanged.

Conclusions

Weekly enzyme infusions slow the decline of renal function in a subgroup of more severe patients thus showing that existing ERT can be further optimized.

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Acknowledgments

This work was supported in part by the Intramural Program of the National Institute of Neurological Disorders and Stroke, by Shire Human Genetic Therapies and the Baylor Healthcare System.

Conflict of interest

Markus Ries was an employee of Shire HGT from 2006 to 2009; he has served on advisory boards for Amicus, Alexion, GSK, and Shire HGT, has received consultancy honoraria from Alexion, Oxyrane, and Shire HGT as well as unrestricted research grants from Shire HGT in compliance with the policy of the Hospital of the University of Heidelberg, Germany. Raphael Schiffmann received research funds and honoraria from Shire HGT and Amicus Therapeutics.

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Authors and Affiliations

  1. Institute of Metabolic Disease, Baylor Research Institute, 3812 Elm Street, Dallas, TX, 75226, USA

    Raphael Schiffmann & Caren Swift

  2. Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, 75246, USA

    Xuan Wang & Derek Blankenship

  3. Pediatric Neurology and Center for Rare Disorders, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

    Markus Ries

Authors
  1. Raphael Schiffmann
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  2. Caren Swift
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  3. Xuan Wang
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  4. Derek Blankenship
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  5. Markus Ries
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Corresponding author

Correspondence to Raphael Schiffmann.

Additional information

Communicated by: Marc Patterson

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Schiffmann, R., Swift, C., Wang, X. et al. A prospective 10-year study of individualized, intensified enzyme replacement therapy in advanced Fabry disease. J Inherit Metab Dis 38, 1129–1136 (2015). https://doi.org/10.1007/s10545-015-9845-5

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  • DOI: https://doi.org/10.1007/s10545-015-9845-5

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