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

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 g...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941144/
https://www.ncbi.nlm.nih.gov/pubmed/26993266
http://dx.doi.org/10.1136/jmedgenet-2015-103486
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author 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
author_facet 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
author_sort Ortiz, Alberto
collection PubMed
description 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.
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spelling pubmed-49411442016-07-13 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 J Med Genet Therapeutics 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. BMJ Publishing Group 2016-07 2016-03-18 /pmc/articles/PMC4941144/ /pubmed/26993266 http://dx.doi.org/10.1136/jmedgenet-2015-103486 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Therapeutics
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
title Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry
title_full Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry
title_fullStr Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry
title_full_unstemmed Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry
title_short Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry
title_sort time to treatment benefit for adult patients with fabry disease receiving agalsidase β: data from the fabry registry
topic Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941144/
https://www.ncbi.nlm.nih.gov/pubmed/26993266
http://dx.doi.org/10.1136/jmedgenet-2015-103486
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