title: Outcomes of patients treated through the Canadian Fabry disease initiative.
abstract: BACKGROUND
  The Canadian Fabry disease initiative (CFDI) tracks outcomes of subjects with Fabry disease treated enzyme replacement therapy (ERT) given to subjects who meet evidence-based treatment guidelines and cardiovascular risk factor modification.
  
  
  METHODS
  We report 5 year follow-up data on 362 subjects for a composite endpoint (death, neurologic or cardiovascular events, development of end-stage renal disease or sustained increase in serum creatinine of 50% from baseline).
  
  
  RESULTS
  At enrollment, 86 subjects had previously received ERT (Cohort 1a) and 67 subjects were newly started (Cohort 1b) and randomized to agalsidase alfa or agalsidase beta. 209 subjects did not initially meet ERT criteria (Cohort 1c), 25 of whom met ERT criteria in follow-up and were moved to Cohort 1b (total N=178 ERT treated subjects). Use of supportive therapies such as aspirin (78%), renin-angiotensin blockade (59%), and statins (55%) was common in ERT treated subjects. In Cohort 1a, 32 subjects met the composite endpoint with 8 deaths. In Cohort 1b, 16 subjects met the composite endpoint with 1 death. Cohort 1b had fewer clinical events than Cohort 1a (p=0.039) suggesting that the treatment protocol was effective in targeting subjects at an earlier stage. 19.4% of Cohort 1b subjects on agalsidase alfa and 13.3% on agalsidase beta had a clinical event (p=0.57). 10 Cohort 1c subjects had clinical events, none of which would have been prevented by earlier use of ERT.
  
  
  CONCLUSIONS
  Cardiovascular risk factor modification and targeted use of ERT reduce the risk of adverse outcomes related to Fabry disease.
authors.affiliation: Department of Medicine University of British Columbia, Canada. Electronic address: Sandra.Sirrs@vch.ca.
authors.forename: S M
authors.initials: SM
authors.lastname: Sirrs
authors.affiliation: Department of Medicine University of Montreal, Canada.
authors.forename: D G
authors.initials: DG
authors.lastname: Bichet
authors.affiliation: Department of Pediatrics University of Calgary, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Casey
authors.affiliation: Department of Pediatrics, Hospital for Sick Children and Centre Hospitalier Universitaire de Sherbrooke, Canada.
authors.forename: J T R
authors.initials: JT
authors.lastname: Clarke
authors.affiliation: Department of Pediatrics, Capital District Health Authority, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Lemoine
authors.affiliation: Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Doucette
authors.affiliation: Department of Medicine Dalhousie University, Canada.
authors.forename: M L
authors.initials: ML
authors.lastname: West
mesh_terms: D000328:Adult; D000368:Aged; D002170:Canada; D002318:Cardiovascular Diseases / Q000209:etiology; D015331:Cohort Studies; D023381:Endpoint Determination; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012307:Risk Factors; D016896:Treatment Outcome; D000519:alpha-Galactosidase / Q000627:therapeutic use
chemical_list: D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase; C459420:agalsidase beta
keywords: Agalsidase; Enzyme replacement therapy; Fabry disease; Outcomes