Maarten Arends1, Frits A Wijburg2, Christoph Wanner3, Frédéric M Vaz4, André B P van Kuilenburg5, Derralynn A Hughes6, Marieke Biegstraaten7, Atul Mehta8, Carla E M Hollak9, Mirjam Langeveld10. 1. Department of Endocrinology and Metabolism, Academic Medical Center, The Netherlands. Electronic address: m.arends@amc.uva.nl. 2. Department of Pediatrics, Academic Medical Center, The Netherlands. Electronic address: f.a.wijburg@amc.uva.nl. 3. Department of Internal Medicine I, Division of Nephrology and Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital Wuerzburg, Germany. Electronic address: wanner_c@ukw.de. 4. Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: f.m.vaz@amc.uva.nl. 5. Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: a.b.vankuilenburg@amc.uva.nl. 6. Department of Haematology, Royal Free London NHS Foundation Trust and University College London, United Kingdom. Electronic address: rmgvdah@ucl.ac.uk. 7. Department of Endocrinology and Metabolism, Academic Medical Center, The Netherlands. Electronic address: m.biegstraaten@amc.uva.nl. 8. Department of Haematology, Royal Free London NHS Foundation Trust and University College London, United Kingdom. Electronic address: atul.mehta1@nhs.net. 9. Department of Endocrinology and Metabolism, Academic Medical Center, The Netherlands. Electronic address: c.e.hollak@amc.uva.nl. 10. Department of Endocrinology and Metabolism, Academic Medical Center, The Netherlands. Electronic address: m.langeveld@amc.uva.nl.
Abstract
BACKGROUND: The level of plasma globotriaosylsphingosine (lysoGb3) is an indication of disease severity in Fabry disease (FD) and its decrease during enzyme replacement therapy could be a reflection of treatment efficacy. Early treatment of FD may improve clinical outcome, but data to support this hypothesis are scarce. In this study we compared lysoGb3 decrease after ERT initiation in men with classical FD who started ERT before the age of 25 (early-treatment) with those who started later in life (late-treatment). METHODS: Treatment naïve men with classical FD from three centers of excellence in Europe were included. Measurements of lysoGb3 levels by tandem mass spectroscopy and antibodies by an inhibitory assay were performed in a single laboratory. Results were adjusted for lysoGb3 at baseline, first ERT (i.e. agalsidase alfa or beta) and the average ERT dose. RESULTS: 85 patients were included, 21 in the early-treatment and 64 in the late-treatment group. LysoGb3 level at baseline was not different between the two groups (112 vs 114nmol/L, p=0.92). The adjusted odds ratio for reaching a lysoGb3 level<20nmol/L was 7.38 for the early-treatment versus late-treatment group (95% CI: 1.91-34.04, p=0.006). The adjusted lysoGb3 levels one year after ERT initiation was 12.9nmol/L lower in the early-treatment (95% CI: -20.1--5.8, p<0.001) compared to the late-treatment group. CONCLUSION: The current retrospective cohort study shows that initiation of ERT at younger age in men with classical Fabry disease results in a better biochemical response.
BACKGROUND: The level of plasma globotriaosylsphingosine (lysoGb3) is an indication of disease severity in Fabry disease (FD) and its decrease during enzyme replacement therapy could be a reflection of treatment efficacy. Early treatment of FD may improve clinical outcome, but data to support this hypothesis are scarce. In this study we compared lysoGb3 decrease after ERT initiation in men with classical FD who started ERT before the age of 25 (early-treatment) with those who started later in life (late-treatment). METHODS: Treatment naïve men with classical FD from three centers of excellence in Europe were included. Measurements of lysoGb3 levels by tandem mass spectroscopy and antibodies by an inhibitory assay were performed in a single laboratory. Results were adjusted for lysoGb3 at baseline, first ERT (i.e. agalsidase alfa or beta) and the average ERT dose. RESULTS: 85 patients were included, 21 in the early-treatment and 64 in the late-treatment group. LysoGb3 level at baseline was not different between the two groups (112 vs 114nmol/L, p=0.92). The adjusted odds ratio for reaching a lysoGb3 level<20nmol/L was 7.38 for the early-treatment versus late-treatment group (95% CI: 1.91-34.04, p=0.006). The adjusted lysoGb3 levels one year after ERT initiation was 12.9nmol/L lower in the early-treatment (95% CI: -20.1--5.8, p<0.001) compared to the late-treatment group. CONCLUSION: The current retrospective cohort study shows that initiation of ERT at younger age in men with classical Fabry disease results in a better biochemical response.
Authors: Daniel Franzen; Sarah R Haile; David C Kasper; Thomas P Mechtler; Andreas J Flammer; Pierre A Krayenbühl; Albina Nowak Journal: BMJ Open Respir Res Date: 2018-04-21
Authors: Olga Azevedo; Miguel F Gago; Gabriel Miltenberger-Miltenyi; Ana Raquel Robles; Maria Antónia Costa; Olga Pereira; Ana Teresa Vide; Gonçalo Castelo Branco; Sónia Simões; Maria José Guimarães; Ana Salgado; Nuno Sousa; Damião Cunha Journal: Mol Genet Metab Rep Date: 2020-02-15