Abstract
BACKGROUND
Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from the α-galactosidase A gene mutations. Enzyme-replacement-therapy (ERT) products for FD currently used include agalsidase alfa and agalsidase beta. There are many reports on efficacy and safety of ERT. However, most of the previous studies are done as a retrospective medical records analysis.
METHODS
The Japan Fabry Research - 002 (JFR-002) was a prospective observational clinical study of 36 ERT-naïve FD patients (14 men and 22 women) at baseline (BL) and after initiation of ERT with agalsidase alfa 0.2 mg/kg every two weeks, a median period 62.5 months. The parameters measured included globotriaosylceramide (Gb3), globotriaosylsphingosine (Lyso-Gb3), left ventricular mass index (LVMI), brain natriuretic peptide (BNP), high-sensitivity troponin I (hs-Trop I), estimated glomerular filtration rate (eGFR), and anti-agalsidase alfa IgG antibody formation.
RESULTS
All parameters remained steady during ERT treatment period. BNP levels in 14 patients whose BL levels were within the normal range (<19.5 pg/mL) remained within the same range, while 22 patients whose BL levels were abnormally high (≥19.5 pg/mL) gradually showed decreased levels after start of ERT. Gb3 and Lyso-Gb3 levels remarkably decreased after the initiation of ERT and remained low.
CONCLUSION
The JFR-002 suggests that agalsidase alfa is effective in maintaining organ function in FD patients, and that the incidence of infusion reactions related to the treatment with agalsidase alfa is low, indicating the good tolerability to this ERT.
TRIAL REGISTRATION
The JFR-002 was retrospectively registered at Japan Medical Association Center for Clinical Trials (Registration number: JMA-IIA00291) on May 19th, 2017.
TY - JOUR
T1 - Efficacy and safety of enzyme-replacement-therapy with agalsidase alfa in 36 treatment-naïve Fabry disease patients.
AU - Tsuboi,Kazuya,
AU - Yamamoto,Hiroshi,
Y1 - 2017/06/07/
PY - 2017/02/24/received
PY - 2017/05/26/accepted
PY - 2017/6/9/entrez
PY - 2017/6/9/pubmed
PY - 2018/4/4/medline
KW - Agalsidase Alfa
KW - Enzyme replacement therapy (ERT)
KW - Fabry disease
KW - Globotriaosylceramide (Gb3)
KW - Globotriaosylsphingosine (lyso-Gb3)
SP - 43
EP - 43
JF - BMC pharmacology & toxicology
JO - BMC Pharmacol Toxicol
VL - 18
IS - 1
N2 - BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from the α-galactosidase A gene mutations. Enzyme-replacement-therapy (ERT) products for FD currently used include agalsidase alfa and agalsidase beta. There are many reports on efficacy and safety of ERT. However, most of the previous studies are done as a retrospective medical records analysis. METHODS: The Japan Fabry Research - 002 (JFR-002) was a prospective observational clinical study of 36 ERT-naïve FD patients (14 men and 22 women) at baseline (BL) and after initiation of ERT with agalsidase alfa 0.2 mg/kg every two weeks, a median period 62.5 months. The parameters measured included globotriaosylceramide (Gb3), globotriaosylsphingosine (Lyso-Gb3), left ventricular mass index (LVMI), brain natriuretic peptide (BNP), high-sensitivity troponin I (hs-Trop I), estimated glomerular filtration rate (eGFR), and anti-agalsidase alfa IgG antibody formation. RESULTS: All parameters remained steady during ERT treatment period. BNP levels in 14 patients whose BL levels were within the normal range (<19.5 pg/mL) remained within the same range, while 22 patients whose BL levels were abnormally high (≥19.5 pg/mL) gradually showed decreased levels after start of ERT. Gb3 and Lyso-Gb3 levels remarkably decreased after the initiation of ERT and remained low. CONCLUSION: The JFR-002 suggests that agalsidase alfa is effective in maintaining organ function in FD patients, and that the incidence of infusion reactions related to the treatment with agalsidase alfa is low, indicating the good tolerability to this ERT. TRIAL REGISTRATION: The JFR-002 was retrospectively registered at Japan Medical Association Center for Clinical Trials (Registration number: JMA-IIA00291) on May 19th, 2017.
SN - 2050-6511
UR - https://www.unboundmedicine.com/medline/citation/28592315/Efficacy_and_safety_of_enzyme_replacement_therapy_with_agalsidase_alfa_in_36_treatment_naïve_Fabry_disease_patients_
L2 - https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-017-0152-7
DB - PRIME
DP - Unbound Medicine
ER -