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2015 ; 3
(ä): 21-7
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Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A
Fabry Outcome Survey analysis
#MMPMID26937390
Beck M
; Hughes D
; Kampmann C
; Larroque S
; Mehta A
; Pintos-Morell G
; Ramaswami U
; West M
; Wijatyk A
; Giugliani R
Mol Genet Metab Rep
2015[Jun]; 3
(ä): 21-7
PMID26937390
show ga
Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement
therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey
(FOS) were compared with published findings for untreated patients with Fabry
disease. Data were extracted from FOS, a Shire-sponsored database, for comparison
with data from three published studies. Outcomes evaluated were the annualized
rate of change in estimated glomerular filtration rate (eGFR) and left
ventricular mass indexed to height (LVMI) as well as time to and ages at a
composite morbidity endpoint and at death. FOS data were extracted for 740
treated patients who were followed for a median of ~ 5 years. Compared with no
treatment, patients treated with agalsidase alfa demonstrated slower decline in
renal function and slower progression of left ventricular hypertrophy. Treated
male patients with baseline eGFR < 60 mL/min/1.73 m(2) had a mean (standard error
of the mean [SEM]) annualized change in eGFR of - 2.86 (0.53) mL/min/1.73 m(2)/y
compared with - 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate
of LVMI increase with treatment was 0.33 (0.10) g/m(2.7)/y in males and 0.48
(0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81)
in untreated females. Morbidity occurred later in treated patients, with ~ 16%
risk of a composite morbidity event (26% in males) after 24 months with ERT
versus ~ 45% without treatment, with first events and deaths also occurring at
older ages in patients administered ERT (e.g., estimated median survival in
treated males was 77.5 years versus 60 years in untreated males). Findings from
these retrospective comparisons of observational data and published literature
support the long-term benefits of ERT with agalsidase alfa for Fabry disease in
slowing the progression of renal impairment and cardiomyopathy. Treatment also
appeared to delay the onset of morbidity and mortality. Interpretation of these
findings should take into account that they are based on retrospective
comparisons with previously published data.