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 Ortiz, Alberto
A1 Abiose, Ademola
A1 Bichet, Daniel G
A1 Cabrera, Gustavo
A1 Charrow, Joel
A1 Germain, Dominique P
A1 Hopkin, Robert J
A1 Jovanovic, Ana
A1 Linhart, Aleš
A1 Maruti, Sonia S
A1 Mauer, Michael
A1 Oliveira, João P
A1 Patel, Manesh R
A1 Politei, Juan
A1 Waldek, Stephen
A1 Wanner, Christoph
A1 Yoo, Han-Wook
A1 Warnock, David G
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.