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See 1 citation in J Med Genet 2016:

J Med Genet. 2016 Jul;53(7):495-502. doi: 10.1136/jmedgenet-2015-103486. Epub 2016 Mar 18.

Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry.

Author information

1
Unidad de Dialisis, IIS-Fundacion Jimenez Diaz/UAM, IRSIN, Madrid, Spain.
2
North Ohio Heart Center, Westlake, Ohio, USA.
3
Hôpital du Sacré-Coeur de Montréal and University of Montreal, Montreal, QC, Canada.
4
Grupo Medico Del Viso, Buenos Aires, Argentina.
5
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.
6
Division of Medical Genetics, University of Versailles-St Quentin en Yvelines, Versailles, France Assistance Publique-Hôpitaux de Paris, Garches, France.
7
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
8
Department of Endocrinology and Metabolic Medicine, Salford Royal NHS Foundation Trust, Salford, UK.
9
Department of Internal Medicine, School of Medicine, Charles University, Prague, Czech Republic.
10
Genzyme, a Sanofi Company, Cambridge, Massachusetts, USA.
11
Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
12
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.
13
Division of Cardiovascular Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
14
Department of Neurology, Fundacion Para el Estudio de Enfermedades Neurometabolicas (FESEN), Buenos Aires, Argentina.
15
University of Sunderland, Sunderland, UK.
16
Division of Nephrology, University Clinic, University of Würzburg, Würzburg, Germany.
17
Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
18
Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

TRIAL REGISTRATION NUMBER:

NCT00196742.

KEYWORDS:

Cardiovascular Medicine; Clinical genetics; Getting Research into Practice

PMID:
26993266
PMCID:
PMC4941144
DOI:
10.1136/jmedgenet-2015-103486
[Indexed for MEDLINE]
Free PMC Article

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