title: Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry.
abstract: Agalsidase β is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase β cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a 'lag time' to clinical benefit after initiating agalsidase β treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase β.
  
  
  
  The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase β (average dose 1 mg/kg every 2 weeks) for up to 5 years.
  
  
  
  The incidence of all severe clinical events was 111 per 1000 person-years (95% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40-58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged ≥40 years when agalsidase β was initiated.
  
  
  
  Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase β 1 mg/kg every 2 weeks.
  
  
  
  NCT00196742.
authors.affiliation: Unidad de Dialisis, IIS-Fundacion Jimenez Diaz/UAM, IRSIN, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: North Ohio Heart Center, Westlake, Ohio, USA.
authors.forename: Ademola
authors.initials: A
authors.lastname: Abiose
authors.affiliation: Hôpital du Sacré-Coeur de Montréal and University of Montreal, Montreal, QC, Canada.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bichet
authors.affiliation: Grupo Medico Del Viso, Buenos Aires, Argentina.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Cabrera
authors.affiliation: Division of Genetics, Birth Defects, and Metabolism, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Charrow
authors.affiliation: Division of Medical Genetics, University of Versailles-St Quentin en Yvelines, Versailles, France Assistance Publique-Hôpitaux de Paris, Garches, France.
authors.forename: Dominique P
authors.initials: DP
authors.lastname: Germain
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hopkin
authors.affiliation: Department of Endocrinology and Metabolic Medicine, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Jovanovic
authors.affiliation: Department of Internal Medicine, School of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Aleš
authors.initials: A
authors.lastname: Linhart
authors.affiliation: Genzyme, a Sanofi Company, Cambridge, Massachusetts, USA.
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Maruti
authors.affiliation: Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mauer
authors.affiliation: Department of Genetics, São João Hospital Centre & Faculty of Medicine, University of Porto, Porto, Portugal I3S-Institute for Research and Innovation in Health, University of Porto, Porto, Portugal.
authors.forename: João P
authors.initials: JP
authors.lastname: Oliveira
authors.affiliation: Division of Cardiovascular Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
authors.affiliation: Department of Neurology, Fundacion Para el Estudio de Enfermedades Neurometabolicas (FESEN), Buenos Aires, Argentina.
authors.forename: Juan
authors.initials: J
authors.lastname: Politei
authors.affiliation: University of Sunderland, Sunderland, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Waldek
authors.affiliation: Division of Nephrology, University Clinic, University of Würzburg, Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.affiliation: Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Han-Wook
authors.initials: HW
authors.lastname: Yoo
authors.affiliation: Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Warnock
mesh_terms: D000328:Adult; D056947:Enzyme Replacement Therapy / Q000379:methods; D000795:Fabry Disease / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006017:Glycolipids / Q000378:metabolism; D006801:Humans; D015994:Incidence; D007527:Isoenzymes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012042:Registries; D061665:Time-to-Treatment; D016896:Treatment Outcome; D000519:alpha-Galactosidase / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D006017:Glycolipids; D007527:Isoenzymes; D000519:alpha-Galactosidase; C459420:agalsidase beta
keywords: Cardiovascular Medicine; Clinical genetics; Getting Research into Practice