Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy: Data from the Fabry Registry

Robert J. Hopkin, Gustavo Cabrera, Joel Charrow, Roberta Lemay, Ana Maria Martins, Michael Mauer, Alberto Ortiz, Manesh R. Patel, Katherine Sims, Stephen Waldek, David G. Warnock, William R. Wilcox

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Background Fabry disease, an X-linked lysosomal storage disorder, causes intracellular accumulation of glycosphingolipids leading to progressive renal, cardiovascular, and cerebrovascular disease, and premature death. Methods This longitudinal Fabry Registry study analyzed data from patients with Fabry disease to determine the incidence and type of severe clinical events following initiation of enzyme replacement therapy (ERT) with agalsidase beta, as well as risk factors associated with occurrence of these events. Severe events assessed included chronic dialysis, renal transplantation, cardiac events, stroke, and death. Results The analyses included 969 male and 442 female Fabry patients. The mean age at first agalsidase beta infusion was 35 and 44, and median treatment follow-up 4.3 years and 3.2 years, respectively. Among males, cardiac events were the most common on-ERT events, followed by renal, stroke, and non-cardiac death. Among females, cardiac events were also most common followed by stroke and renal events. Patients with on-ERT events had significantly more advanced cardiac and renal disease at baseline as compared with patients without on-ERT events. Severe events were also associated with older age at ERT initiation (males and females), a history of pre-ERT events (females; approaching statistical significance in males), and a higher urinary protein/creatinine ratio (females). Approximately 65% of patients with pre-ERT events did not experience subsequent on-ERT events. Of patients without pre-ERT events, most (84% of males, 92% of females) remained event-free. Conclusions Patients with on-ERT severe events had more advanced Fabry organ involvement at baseline than those without such events and patients who initiated ERT at a younger age had less residual risk of on-ERT events. The observed patterns of residual risk may aid clinicians in multidisciplinary monitoring of male and female patients with Fabry disease receiving ERT, and in determining the need for administration of adjunctive therapies.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalMolecular Genetics and Metabolism
Issue number1-2
StatePublished - Sep 1 2016

Bibliographical note

Funding Information:
The authors would like to thank the many patients who have agreed to participate in the Fabry Registry as well as the physicians and research coordinators who have entered clinical data on behalf of these patients. We also acknowledge Pr. Dr. Jörg Strotmann, for input on the methodology and analysis plans, and Badari Gudivada (Sanofi Genzyme), for statistical programming support. We thank Cheryl Lathrop and Hans Ebels for providing medical writing/editing services on behalf of Sanofi Genzyme. A.O. was supported by ISCIII intensificación de la actividad investigadora. The authors received submission assistance provided by Alessia Piazza of Excerpta Medica, funded by Sanofi Genzyme .

Funding Information:
S.W. has consulted for Sanofi Genzyme and Shire HGT. In the past, he has received research funding from Sanofi Genzyme, Shire HGT, Amicus Therapeutics, and BioMarin Pharmaceuticals. He has also received funding for travel and presenting at meetings.

Funding Information:
K.S. is an investigator for clinical trials sponsored by Amicus Therapeutics and receives research funding from Sanofi Genzyme. These interests have been reviewed and managed by the Massachusetts General Hospital in accordance with its conflict of interest policy.

Publisher Copyright:
© 2016 The Authors

Copyright 2017 Elsevier B.V., All rights reserved.


  • Agalsidase beta
  • Fabry disease
  • Risk factors
  • Severe clinical events

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