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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.
Mol Genet Metab. 2016 09; 119(1-2):151-9.MG

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 4.3years and 3.2years, 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.

Authors+Show Affiliations

Cincinnati Children's Hospital Medical Center, Cincinnati, USA; Department of Pediatrics, University of Cincinnati College Medicine, Cincinnati, USA. Electronic address: rob.hopkin@cchmc.org.Centro Cardiovascular Bolivar, Buenos Aires, Argentina. Electronic address: gustavo.h.cabrera@hotmail.com.Division of Genetics, Birth Defects and Metabolism, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, USA. Electronic address: jcharrow@northwestern.edu.Strategic Epidemiology & Biostatistics, Rare Diseases, Sanofi Genzyme, Cambridge, USA. Electronic address: Roberta.Lemay@genzyme.com.Reference Center for Inborn Errors of Metabolism, Federal University of São Paulo, São Paulo, Brazil. Electronic address: martins.anamaria@uol.com.br.Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, USA. Electronic address: mauer002@umn.edu.Unidad de Dialisis, IIS-Fundacion Jimenez Diaz, School of Medicine, UAM, IRSIN, REDINREN, Madrid, Spain. Electronic address: AOrtiz@fjd.es.Division of Cardiovascular Medicine, Duke University School of Medicine, Durham, USA. Electronic address: patel017@mc.duke.edu.Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, USA. Electronic address: Sims@Helix.MGH.Harvard.edu.University of Sunderland, Sunderland, United Kingdom. Electronic address: stephen.waldek@sunderland.ac.uk.Division of Nephrology, University of Alabama at Birmingham, Birmingham, USA. Electronic address: dwarnock@uab.edu.Division of Medical Genetics, Department of Human Genetics, Emory University School of Medicine, Atlanta, USA. Electronic address: william.wilcox@emory.edu.

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27510433

Citation

Hopkin, Robert J., et al. "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." Molecular Genetics and Metabolism, vol. 119, no. 1-2, 2016, pp. 151-9.
Hopkin RJ, Cabrera G, Charrow J, et al. 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. Mol Genet Metab. 2016;119(1-2):151-9.
Hopkin, R. J., Cabrera, G., Charrow, J., Lemay, R., Martins, A. M., Mauer, M., Ortiz, A., Patel, M. R., Sims, K., Waldek, S., Warnock, D. G., & Wilcox, W. R. (2016). 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. Molecular Genetics and Metabolism, 119(1-2), 151-9. https://doi.org/10.1016/j.ymgme.2016.06.007
Hopkin RJ, et al. 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. Mol Genet Metab. 2016;119(1-2):151-9. PubMed PMID: 27510433.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. 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, Y1 - 2016/06/13/ PY - 2016/04/26/received PY - 2016/06/10/revised PY - 2016/06/10/accepted PY - 2016/8/12/entrez PY - 2016/8/12/pubmed PY - 2017/12/8/medline KW - Agalsidase beta KW - Fabry disease KW - Risk factors KW - Severe clinical events SP - 151 EP - 9 JF - Molecular genetics and metabolism JO - Mol. Genet. Metab. VL - 119 IS - 1-2 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 4.3years and 3.2years, 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. SN - 1096-7206 UR - https://www.unboundmedicine.com/medline/citation/27510433/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(16)30115-9 DB - PRIME DP - Unbound Medicine ER -