TY - JOUR
T1 - Early start of enzyme replacement therapy in pediatric male patients with classical Fabry disease is associated with attenuated disease progression
AU - van der Veen, S J
AU - Körver, S
AU - Hirsch, A
AU - Hollak, C E M
AU - Wijburg, F A
AU - Brands, M M
AU - Tøndel, C
AU - van Kuilenburg, A B P
AU - Langeveld, M
N1 - Funding Information: M. Langeveld and C.E. Hollak are involved in pre-marketing studies with Sanofi-Genzyme, Protalix and Idorsia. Financial arrangements are made through AMC Research BV. S. van der Veen is involved in a premarketing study with Protalix. Financial arrangements are made through AMC Research BV. F. Wijburg has received speaker honoraria and travel support from Sanofi/Genzyme and Shire; has participated in studies supported by Sanofi Genzyme and Shire. A. Hirsch has received a speaker fee and travel support from Sanovi-Genzyme. C. Tøndel has received honoraria and travel support from Sanofi Genzyme, Amicus and Shire; has participated in studies supported by Protalix, Sanofi Genzyme, Idorsia, Freeline, Amicus and Shire. S. Korver, M.M. Brands and A.B.P. van Kuilenburg declare that they have no conflict of interest. No fees, travel support or grants are obtained from Pharmaceutical Industry in relation to the submitted work. Funding Information: This research was funded by SPHINX, the Amsterdam Lysosome Center. Funding Information: This research was funded by SPHINX, the Amsterdam Lysosome Center.An additional grant (clinical research matching grant 2020) was generously awarded by the Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) research board. Publisher Copyright: © 2021 The Authors
PY - 2022/2/1
Y1 - 2022/2/1
N2 - Background: Enzyme replacement therapy (ERT) slows disease progression of Fabry disease (FD), especially when initiated before the onset of irreversible organ damage. However, with the clinically asymptomatic progression of renal, cardiac and cerebral disease manifestations spanning decades, optimal timing of ERT initiation remains unclear. Methods: In this cross-sectional retrospective study, seven male FD patients with a classical disease phenotype (cFD) who started treatment with agalsidase-beta in childhood were evaluated after 10 years of treatment (median age at evaluation 24 years, range 14–26). Cardiac imaging (echocardiography and MRI), electrophysiological and biochemical data of these patients were compared to those of untreated male cFD patients (n = 23, median age 22 years, range 13–27). Results: Albuminuria was less common and less severe in treated patients (albumin to creatinine ratio, ACR 0–8.8 mg/mmol, median 0.4) compared to untreated patients (ACR 0–248 mg/mmol, median 3.7, p = 0.02). The treated group had a lower left ventricular mass, measured using echocardiography (median 80 g/m2 versus 94 g/m2, p = 0.02) and MRI (median 53 g/m2 versus 68 g/m2, p = 0.02). Myocardial fibrosis was absent in all included patients. eGFR was normal in all treated patients whereas 7/23 (30%) of untreated patients had abnormal eGFR. Cerebral manifestations did not differ. Conclusions: Start of treatment with ERT before age 16, in male cFD patients is associated with reduced occurrence of renal and cardiac manifestations of FD, as assessed by intermediate endpoints. Confirmation that this approach delays or even prevents renal failure and cardiac events requires another decade of follow-up.
AB - Background: Enzyme replacement therapy (ERT) slows disease progression of Fabry disease (FD), especially when initiated before the onset of irreversible organ damage. However, with the clinically asymptomatic progression of renal, cardiac and cerebral disease manifestations spanning decades, optimal timing of ERT initiation remains unclear. Methods: In this cross-sectional retrospective study, seven male FD patients with a classical disease phenotype (cFD) who started treatment with agalsidase-beta in childhood were evaluated after 10 years of treatment (median age at evaluation 24 years, range 14–26). Cardiac imaging (echocardiography and MRI), electrophysiological and biochemical data of these patients were compared to those of untreated male cFD patients (n = 23, median age 22 years, range 13–27). Results: Albuminuria was less common and less severe in treated patients (albumin to creatinine ratio, ACR 0–8.8 mg/mmol, median 0.4) compared to untreated patients (ACR 0–248 mg/mmol, median 3.7, p = 0.02). The treated group had a lower left ventricular mass, measured using echocardiography (median 80 g/m2 versus 94 g/m2, p = 0.02) and MRI (median 53 g/m2 versus 68 g/m2, p = 0.02). Myocardial fibrosis was absent in all included patients. eGFR was normal in all treated patients whereas 7/23 (30%) of untreated patients had abnormal eGFR. Cerebral manifestations did not differ. Conclusions: Start of treatment with ERT before age 16, in male cFD patients is associated with reduced occurrence of renal and cardiac manifestations of FD, as assessed by intermediate endpoints. Confirmation that this approach delays or even prevents renal failure and cardiac events requires another decade of follow-up.
KW - Disease phenotype
KW - Early treatment
KW - Enzyme replacement therapy
KW - Fabry disease
UR - http://www.scopus.com/inward/record.url?scp=85122967021&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ymgme.2021.12.004
DO - https://doi.org/10.1016/j.ymgme.2021.12.004
M3 - Article
C2 - 35033446
SN - 1096-7192
VL - 135
SP - 163
EP - 169
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 2
ER -