TY  - JOUR
A1  - Ortiz, Alberto
A1  - Abiose, Ademola
A1  - Bichet, Daniel G.
A1  - Cabrera, Gustavo
A1  - Charrow, Joel
A1  - Germain, Dominique P.
A1  - Hopkin, Robert J.
A1  - Jovanovic, Ana
A1  - Linhart, Aleš
A1  - Maruti, Sonia S.
A1  - Mauer, Michael
A1  - Oliveira, João P.
A1  - Patel, Manesh R.
A1  - Politei, Juan
A1  - Waldek, Stephen
A1  - Wanner, Christoph
A1  - Yoo, Han-Wook
A1  - Warnock, David G.
T1  - Time to treatment benefit for adult patients with Fabry disease receiving agalsidase beta: data from the Fabry Registry
JF  - Journal of Medical Genetics
N2  - Background 
Agalsidase beta is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low alpha-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase beta 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 beta treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase beta. 

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 beta (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 beta 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 beta 1 mg/kg every 2 weeks.
KW  - Enzyme replacement therapy
KW  - Natural-history data
KW  - Racial differences
KW  - Outcome survey
KW  - Galactosidase-A gene
KW  - Alpha-Galactosidase
KW  - Kidney function
KW  - Lag time
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188241
VL  - 53
IS  - 7
ER  - 
TY  - JOUR
A1  - Warnock, David G.
A1  - Ortiz, Alberto
A1  - Mauer, Michael
A1  - Linthorst, Gabor E.
A1  - Oliveira, João P.
A1  - Serra, Andreas L.
A1  - Maródi, László
A1  - Mignani, Renzo
A1  - Vujkovac, Bojan
A1  - Beitner-Johnson, Dana
A1  - Lemay, Roberta
A1  - Cole, J. Alexander
A1  - Svarstad, Einar
A1  - Waldek, Stephen
A1  - Germain, Dominique P.
A1  - Wanner, Christoph
T1  - Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation
JF  - Nephrology Dialysis Transplantation
N2  - Background. The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta.

Methods. Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment. Multivariate logistic regression analyses were used to identify factors associated with renal disease progression.

Results. Men within the first quartile had a mean eGFR slope of –0.1 mL/min/1.73m2/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of –6.7 mL/min/1.73m2/year. The risk factor most strongly associated with renal disease progression was averaged urinary protein:creatinine ratio (UP/Cr) ≥1 g/g (odds ratio 112, 95% confidence interval (95% CI) 4–3109, P = 0.0054). Longer time from symptom onset to treatment was also associated with renal disease progression (odds ratio 19, 95% CI 2–184, P = 0.0098). Women in Quartile 4 had the highest averaged UP/Cr (mean 1.8 g/g) and the most rapid renal disease progression: (mean slope –4.4 mL/min/1.73m2/year).

Conclusions. Adults with Fabry disease are at risk for progressive loss of eGFR despite enzyme replacement therapy, particularly if proteinuria is ≥1 g/g. Men with little urinary protein excretion and those who began receiving agalsidase beta sooner after the onset of symptoms had stable renal function. These findings suggest that early intervention may lead to optimal renal outcomes.
KW  - proteinuria
KW  - enzyme replacement therapy
KW  - alpha galactosidase
KW  - Fabry disease
KW  - genetic renal disease
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124697
VL  - 27
IS  - 3
ER  -