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 journalArticle

7 Citations (Scopus)

Abstract

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
Volume119
Issue number1-2
DOIs
StatePublished - Sep 1 2016

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Enzyme Replacement Therapy
Fabry Disease
Registries
Enzymes
Kidney
Stroke
agalsidase beta
Cerebrovascular Disorders
Glycosphingolipids
Premature Mortality
Dialysis
Kidney Transplantation

Keywords

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

Cite this

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

In: Molecular Genetics and Metabolism, Vol. 119, No. 1-2, 01.09.2016, p. 151-159.

Research output: Contribution to journalArticle

Hopkin, Robert J. ; Cabrera, Gustavo ; Charrow, Joel ; Lemay, Roberta ; Martins, Ana Maria ; Mauer, Michael ; Ortiz, Alberto ; Patel, Manesh R. ; Sims, Katherine ; Waldek, Stephen ; Warnock, David G. ; Wilcox, William R. / 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. In: Molecular Genetics and Metabolism. 2016 ; Vol. 119, No. 1-2. pp. 151-159.
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abstract = "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.",
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T1 - Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy

T2 - Data from the Fabry Registry

AU - Hopkin, Robert J.

AU - Cabrera, Gustavo

AU - Charrow, Joel

AU - Lemay, Roberta

AU - Martins, Ana Maria

AU - Mauer, Michael

AU - Ortiz, Alberto

AU - Patel, Manesh R.

AU - Sims, Katherine

AU - Waldek, Stephen

AU - Warnock, David G.

AU - Wilcox, William R.

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N2 - 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.

AB - 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.

KW - Agalsidase beta

KW - Fabry disease

KW - Risk factors

KW - Severe clinical events

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