Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β

Data from the Fabry Registry

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

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background Agalsidase ß 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 ß 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 ß treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase ß. 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 ß (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 ß 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 ß 1 mg/kg every 2 weeks. Trial registration number NCT00196742.

Original languageEnglish (US)
Pages (from-to)495-502
Number of pages8
JournalJournal of medical genetics
Volume53
Issue number7
DOIs
StatePublished - Jul 1 2016

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Fabry Disease
Registries
Incidence
Therapeutics
Galactosidases
Enzyme Replacement Therapy
Glycosphingolipids
Inborn Genetic Diseases
Glycolipids
Renal Insufficiency
Endothelial Cells
Stroke
Clinical Trials
Kidney

Cite this

Ortiz, A., Abiose, A., Bichet, D. G., Cabrera, G., Charrow, J., Germain, D. P., ... Warnock, D. G. (2016). Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: Data from the Fabry Registry. Journal of medical genetics, 53(7), 495-502. https://doi.org/10.1136/jmedgenet-2015-103486

Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β : Data from the Fabry Registry. / Ortiz, Alberto; Abiose, Ademola; Bichet, Daniel G.; Cabrera, Gustavo; Charrow, Joel; Germain, Dominique P.; Hopkin, Robert J.; Jovanovic, Ana; Linhart, Aleš; Maruti, Sonia S.; Mauer, Michael; Oliveira, João P.; Patel, Manesh R.; Politei, Juan; Waldek, Stephen; Wanner, Christoph; Yoo, Han Wook; Warnock, David G.

In: Journal of medical genetics, Vol. 53, No. 7, 01.07.2016, p. 495-502.

Research output: Contribution to journalArticle

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, HW & Warnock, DG 2016, 'Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: Data from the Fabry Registry', Journal of medical genetics, vol. 53, no. 7, pp. 495-502. https://doi.org/10.1136/jmedgenet-2015-103486
Ortiz, Alberto ; Abiose, Ademola ; Bichet, Daniel G. ; Cabrera, Gustavo ; Charrow, Joel ; Germain, Dominique P. ; Hopkin, Robert J. ; Jovanovic, Ana ; Linhart, Aleš ; Maruti, Sonia S. ; Mauer, Michael ; Oliveira, João P. ; Patel, Manesh R. ; Politei, Juan ; Waldek, Stephen ; Wanner, Christoph ; Yoo, Han Wook ; Warnock, David G. / Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β : Data from the Fabry Registry. In: Journal of medical genetics. 2016 ; Vol. 53, No. 7. pp. 495-502.
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T1 - Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β

T2 - Data from the Fabry Registry

AU - Ortiz, Alberto

AU - Abiose, Ademola

AU - Bichet, Daniel G.

AU - Cabrera, Gustavo

AU - Charrow, Joel

AU - Germain, Dominique P.

AU - Hopkin, Robert J.

AU - Jovanovic, Ana

AU - Linhart, Aleš

AU - Maruti, Sonia S.

AU - Mauer, Michael

AU - Oliveira, João P.

AU - Patel, Manesh R.

AU - Politei, Juan

AU - Waldek, Stephen

AU - Wanner, Christoph

AU - Yoo, Han Wook

AU - Warnock, David G.

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N2 - Background Agalsidase ß 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 ß 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 ß treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase ß. 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 ß (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 ß 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 ß 1 mg/kg every 2 weeks. Trial registration number NCT00196742.

AB - Background Agalsidase ß 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 ß 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 ß treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase ß. 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 ß (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 ß 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 ß 1 mg/kg every 2 weeks. Trial registration number NCT00196742.

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