RT Journal Article
SR Electronic
T1 Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 495
OP 502
DO 10.1136/jmedgenet-2015-103486
VO 53
IS 7
A1 Alberto Ortiz
A1 Ademola Abiose
A1 Daniel G Bichet
A1 Gustavo Cabrera
A1 Joel Charrow
A1 Dominique P Germain
A1 Robert J Hopkin
A1 Ana Jovanovic
A1 Aleš Linhart
A1 Sonia S Maruti
A1 Michael Mauer
A1 João P Oliveira
A1 Manesh R Patel
A1 Juan Politei
A1 Stephen Waldek
A1 Christoph Wanner
A1 Han-Wook Yoo
A1 David G Warnock
YR 2016
UL http://jmg.bmj.com/content/53/7/495.abstract
AB 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.