title: 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.
abstract: Fabry disease, an X-linked lysosomal storage disorder, causes intracellular accumulation of glycosphingolipids leading to progressive renal, cardiovascular, and cerebrovascular disease, and premature death.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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: Cincinnati Children's Hospital Medical Center, Cincinnati, USA; Department of Pediatrics, University of Cincinnati College Medicine, Cincinnati, USA. Electronic address: rob.hopkin@cchmc.org.
authors: Robert J
authors: RJ
authors: Hopkin
authors: Centro Cardiovascular Bolivar, Buenos Aires, Argentina. Electronic address: gustavo.h.cabrera@hotmail.com.
authors: Gustavo
authors: G
authors: Cabrera
authors: Division of Genetics, Birth Defects and Metabolism, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, USA. Electronic address: jcharrow@northwestern.edu.
authors: Joel
authors: J
authors: Charrow
authors: Strategic Epidemiology & Biostatistics, Rare Diseases, Sanofi Genzyme, Cambridge, USA. Electronic address: Roberta.Lemay@genzyme.com.
authors: Roberta
authors: R
authors: Lemay
authors: Reference Center for Inborn Errors of Metabolism, Federal University of São Paulo, São Paulo, Brazil. Electronic address: martins.anamaria@uol.com.br.
authors: Ana Maria
authors: AM
authors: Martins
authors: Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, USA. Electronic address: mauer002@umn.edu.
authors: Michael
authors: M
authors: Mauer
authors: Unidad de Dialisis, IIS-Fundacion Jimenez Diaz, School of Medicine, UAM, IRSIN, REDINREN, Madrid, Spain. Electronic address: AOrtiz@fjd.es.
authors: Alberto
authors: A
authors: Ortiz
authors: Division of Cardiovascular Medicine, Duke University School of Medicine, Durham, USA. Electronic address: patel017@mc.duke.edu.
authors: Manesh R
authors: MR
authors: Patel
authors: Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, USA. Electronic address: Sims@Helix.MGH.Harvard.edu.
authors: Katherine
authors: K
authors: Sims
authors: University of Sunderland, Sunderland, United Kingdom. Electronic address: stephen.waldek@sunderland.ac.uk.
authors: Stephen
authors: S
authors: Waldek
authors: Division of Nephrology, University of Alabama at Birmingham, Birmingham, USA. Electronic address: dwarnock@uab.edu.
authors: David G
authors: DG
authors: Warnock
authors: Division of Medical Genetics, Department of Human Genetics, Emory University School of Medicine, Atlanta, USA. Electronic address: william.wilcox@emory.edu.
authors: William R
authors: WR
authors: Wilcox
mesh_terms: D000328:Adult; D002648:Child; D056947:Enzyme Replacement Therapy / Q000009:adverse effects; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000008:administration & dosage* / Q000009:adverse effects; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012042:Registries; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D000519:alpha-Galactosidase / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D007527:Isoenzymes; D000519:alpha-Galactosidase; C459420:agalsidase beta
keywords: Agalsidase beta; Fabry disease; Risk factors; Severe clinical events