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

TLDR

Fabry disease is a genetic disorder caused by deficient α‑galactosidase A, leading to glycosphingolipid accumulation and life‑threatening cardiovascular, renal, and cerebrovascular events, and enzyme replacement therapy with agalsidase β can clear glycolipid deposits from endothelial cells within six months, though clearance from other cell types requires sustained treatment. The study aimed to test whether a lag time exists before clinical benefit of agalsidase β becomes evident by analyzing severe clinical event incidence over time in adult Fabry patients. The authors examined severe clinical event incidence in 1,044 adult Fabry patients receiving 1 mg/kg agalsidase β every two weeks, following them for up to five years in the Fabry Registry. After six months of treatment, the incidence of severe events fell to 40–58 per 1,000 patient‑years and remained stable, with the greatest reductions seen in male patients and those aged 40 years or older.

Abstract

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.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.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.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.NCT00196742.