TY  - JOUR
A1  - Wanner, Christoph
A1  - Feldt-Rasmussen, Ulla
A1  - Jovanovic, Ana
A1  - Linhart, Aleš
A1  - Yang, Meng
A1  - Ponce, Elvira
A1  - Brand, Eva
A1  - Germain, Dominique P.
A1  - Hughes, Derralynn A.
A1  - Jefferies, John L.
A1  - Martins, Anna Maria
A1  - Nowak, Albina
A1  - Vujkovac, Bojan
A1  - Weidemann, Frank
A1  - West, Michael L.
A1  - Ortiz, Alberto
T1  - Cardiomyopathy and kidney function in agalsidase beta-treated female Fabry patients: a pre-treatment vs. post-treatment analysis
JF  - ESC Heart Failure
N2  - Long-term treatment effect studies in large female Fabry patient groups are challenging to design because of phenotype heterogeneity and lack of appropriate comparison groups, and have not been reported. We compared long-term cardiomyopathy and kidney function outcomes after agalsidase beta treatment with preceding treatment-naive outcomes.
Methods and results Self-controlled pretreatment and post-treatment comparison (piecewise mixed linear modelling) included Fabry female patients ≥18 years at treatment initiation who received agalsidase beta (0.9–1.1 mg/kg every other week) for ≥2 years, with ≥2 pretreatment and ≥2 post-treatment outcome measurements during 10-year follow-up. Left ventricular posterior wall thickness (LVPWT)/interventricular septal thickness (IVST) and estimated glomerular filtration rate (eGFR, Chronic Kidney Disease Epidemiology Collaboration creatinine equation) analyses included 42 and 86 patients, respectively, aged 50.0 and 46.3 years at treatment initiation, respectively. LVPWT and IVST increased pretreatment (follow-up 3.5 years) but stabilized during 3.6 years of treatment (LVPWT: n = 38, slope difference [95% confidence interval (CI)] = - 0.41 [ - 0.68, - 0.15] mm/year, P\(_{pre–post difference}\)<0.01; IVST: n = 38, slope difference =-0.32 [-0.67, 0.02] mm/year, P\(_{pre–post difference}\) = 0.07). These findings were not modified by renal involvement or antiproteinuric agent use. Compared with the treatment-naive period (follow-up 3.6 years), eGFR decline remained modest and stabilized within normal ranges during 4.1 years of treatment (slope difference, 95% CI: -0.13 [-1.15, 0.89] mL/min/1.73m\(^2\)/year, P\(_{pre–post difference}\) = 0.80).
Conclusions Cardiac hypertrophy, progressing during pretreatment follow-up, appeared to stabilize during sustained agalsidase beta treatment. eGFR decline remained within normal ranges. This suggests that treatment may prevent further Fabry-related progression of cardiomyopathy in female patients and maintain normal kidney function.
KW  - Agalsidase beta
KW  - Enzyme replacement therapy
KW  - Fabry disease
KW  - Cardiomyopathy
KW  - Kidney function
KW  - Female patients
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235963
VL  - 7
IS  - 3
ER  - 
TY  - JOUR
A1  - Biegstraaten, Marieke
A1  - Arngrímsson, Reynir
A1  - Barbey, Frederic
A1  - Boks, Lut
A1  - Cecchi, Franco
A1  - Deegan, Patrick B
A1  - Feldt-Rasmussen, Ulla
A1  - Geberhiwot, Tarekegn
A1  - Germain, Dominique P
A1  - Hendriksz, Chris
A1  - Hughes, Derralynn A
A1  - Kantola, Ilkka
A1  - Karabul, Nesrin
A1  - Lavery, Christine
A1  - Linthorst, Gabor E
A1  - Mehta, Atul
A1  - van de Mheen, Erica
A1  - Oliveira, João P
A1  - Parini, Rossella
A1  - Ramaswami, Uma
A1  - Rudnicki, Michael
A1  - Serra, Andreas
A1  - Sommer, Claudia
A1  - Sunder-Plassmann, Gere
A1  - Svarstad, Einar
A1  - Sweeb, Annelies
A1  - Terryn, Wim
A1  - Tylki-Szymanska, Anna
A1  - Tøndel, Camilla
A1  - Vujkovac, Bojan
A1  - Weidemann, Frank
A1  - Wijburg, Frits A
A1  - Woolfson, Peter
A1  - Hollak, Carla EM
T1  - Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document
JF  - Orphanet Journal of Rare Diseases
N2  - Introduction:
Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD.

Methods:
A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations were accepted with ≥75% agreement and no disagreement.

Results:
For classically affected males, consensus was achieved that ERT is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients of ≥16 years in the absence of clinical signs or symptoms of organ involvement. Classically affected females and males with non-classical FD should be treated as soon as there are early clinical signs of kidney, heart or brain involvement, while treatment may be considered in females with non-classical FD with early clinical signs that are considered to be due to FD. Consensus was achieved that treatment should not be withheld from patients with severe renal insufficiency (GFR < 45 ml/min/1.73 m\(^{2}\)) and from those on dialysis or with cognitive decline, but carefully considered on an individual basis. Stopping ERT may be considered in patients with end stage FD or other co-morbidities, leading to a life expectancy of <1 year. In those with cognitive decline of any cause, or lack of response for 1 year when the sole indication for ERT is neuropathic pain, stopping ERT may be considered. Also, in patients with end stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV), cessation of ERT should be considered. ERT in patients who are non-compliant or fail to attend regularly at visits should be stopped.

Conclusion:
The recommendations can be used as a benchmark for initiation and cessation of ERT, although final decisions should be made on an individual basis. Future collaborative efforts are needed for optimization of these recommendations.
KW  - Fabry disease
KW  - enzyme replacement therapy
KW  - recommendations
KW  - Delphi procedure
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175374
VL  - 10
IS  - 36
ER  -