title: A prospective 10-year study of individualized, intensified enzyme replacement therapy in advanced Fabry disease.
abstract: OBJECTIVE
  To test the hypothesis that more frequent enzyme replacement therapy (ERT) slows the decline in kidney function in adult patients with Fabry disease.
  
  
  METHODS
  A single center open label 10-year prospective clinical trial of 12 patients with advanced Fabry disease who, after having experienced an ongoing decline in renal function after 2-4 years of receiving ERT at the approved dose of 0.2 mg/kg agalsidase alfa every other week (EOW), were switched to weekly (EW) ERT at the same dose. We used linear regression to fit each individual patient's longitudinal estimated glomerular filtration rate (eGFR) record in order to compare the deterioration rates between EOW and EW ERT.
  
  
  RESULTS
  For the entire group, mean slope on agalsidase alfa every 2 weeks was -7.92 ± 2.88 ml/min/1.73 m(2)/year and 3.84 ± 4.08 ml/min/1.73 m(2)/year on weekly enzyme infusions (p = 0.01, two-tailed paired t test). Three patients (25 %) completed the entire study with relatively preserved renal function while 50 % of patients reached end-stage renal disease (ESRD) during the 10 years of this study. The estimated average delay to ESRD was 13.8 years [n = 11; 95 % CI 0.66, 27]. One patient had a positive eGFR slope on weekly infusions while the patient with the highest antibody titer had a steeper slope after switching. Mean globotriaosylceramide concentrations in urine and plasma as well as urine protein excretion remained unchanged.
  
  
  CONCLUSIONS
  Weekly enzyme infusions slow the decline of renal function in a subgroup of more severe patients thus showing that existing ERT can be further optimized.
authors.affiliation: Institute of Metabolic Disease, Baylor Research Institute, 3812 Elm Street, Dallas, TX, 75226, USA. raphael.schiffmann@baylorhealth.edu.
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.affiliation: Institute of Metabolic Disease, Baylor Research Institute, 3812 Elm Street, Dallas, TX, 75226, USA.
authors.forename: Caren
authors.initials: C
authors.lastname: Swift
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, 75246, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, 75246, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Blankenship
authors.affiliation: Pediatric Neurology and Center for Rare Disorders, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Ries
mesh_terms: D000328:Adult; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000188:drug therapy*; D005919:Glomerular Filtration Rate; D006801:Humans; D007527:Isoenzymes / Q000008:administration & dosage / Q000009:adverse effects; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins; D014281:Trihexosylceramides / Q000097:blood* / Q000652:urine*; D014481:United States; D055815:Young Adult; D000519:alpha-Galactosidase / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D007527:Isoenzymes; D011994:Recombinant Proteins; D014281:Trihexosylceramides; C000627036:agalsidase alfa; C018549:globotriaosylceramide; D000519:alpha-Galactosidase