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

Journal Article (Clinical Trial;Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Ortiz, A; Abiose, A; Bichet, DG; Cabrera, G; Charrow, J; Germain, DP; Hopkin, RJ; Jovanovic, A; Linhart, A; Maruti, SS; Mauer, M; Oliveira, JP; Patel, MR; Politei, J; Waldek, S; Wanner, C; Yoo, H-W; Warnock, DG

Published Date

  • July 2016

Published In

Volume / Issue

  • 53 / 7

Start / End Page

  • 495 - 502

PubMed ID

  • 26993266

Pubmed Central ID

  • PMC4941144

Electronic International Standard Serial Number (EISSN)

  • 1468-6244

Digital Object Identifier (DOI)

  • 10.1136/jmedgenet-2015-103486


  • eng

Conference Location

  • England