Journal Article

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

Germain, Dominique P, Wanner, Christoph, Warnock, David G, Bichet, Daniel G, Charrow, Joel, Yoo, Han-Wook, Oliveira, João P, Abiose, Ademola, Jovanovic, Ana, Maruti, Sonia S, Cabrera, Gustavo, Mauer, Michael, Patel, Manesh R, Linhart, Aleš, Ortiz, Alberto, Politei, Juan, Hopkin, Robert J, Waldek, Stephen

2016

Overview

BackgroundAgalsidase 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.MethodsThe 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.ResultsThe 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.ConclusionsContrary 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 numberNCT00196742.

• Publisher: BMJ Publishing Group
• Subject: Adult / alpha-Galactosidase - metabolism / alpha-Galactosidase - therapeutic use / Enzyme Replacement Therapy - methods / Fabry Disease - drug therapy / Fabry Disease - metabolism / Female / Glycolipids - metabolism / Humans / Incidence / Isoenzymes - therapeutic use / Male / Middle Aged / Registries / Therapeutics / Time-to-Treatment / Treatment Outcome