@article{BiegstraatenArngrimssonBarbeyetal.2015, author = {Biegstraaten, Marieke and Arngr{\´i}msson, Reynir and Barbey, Frederic and Boks, Lut and Cecchi, Franco and Deegan, Patrick B and Feldt-Rasmussen, Ulla and Geberhiwot, Tarekegn and Germain, Dominique P and Hendriksz, Chris and Hughes, Derralynn A and Kantola, Ilkka and Karabul, Nesrin and Lavery, Christine and Linthorst, Gabor E and Mehta, Atul and van de Mheen, Erica and Oliveira, Jo{\~a}o P and Parini, Rossella and Ramaswami, Uma and Rudnicki, Michael and Serra, Andreas and Sommer, Claudia and Sunder-Plassmann, Gere and Svarstad, Einar and Sweeb, Annelies and Terryn, Wim and Tylki-Szymanska, Anna and T{\o}ndel, Camilla and Vujkovac, Bojan and Weidemann, Frank and Wijburg, Frits A and Woolfson, Peter and Hollak, Carla EM}, title = {Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document}, series = {Orphanet Journal of Rare Diseases}, volume = {10}, journal = {Orphanet Journal of Rare Diseases}, number = {36}, doi = {10.1186/s13023-015-0253-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175374}, year = {2015}, abstract = {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.}, language = {en} } @article{WarnockOrtizMaueretal.2012, author = {Warnock, David G. and Ortiz, Alberto and Mauer, Michael and Linthorst, Gabor E. and Oliveira, Jo{\~a}o P. and Serra, Andreas L. and Mar{\´o}di, L{\´a}szl{\´o} and Mignani, Renzo and Vujkovac, Bojan and Beitner-Johnson, Dana and Lemay, Roberta and Cole, J. Alexander and Svarstad, Einar and Waldek, Stephen and Germain, Dominique P. and Wanner, Christoph}, title = {Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation}, series = {Nephrology Dialysis Transplantation}, volume = {27}, journal = {Nephrology Dialysis Transplantation}, number = {3}, organization = {Fabry Registry}, doi = {10.1093/ndt/gfr420}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124697}, pages = {1042-1049}, year = {2012}, abstract = {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.}, language = {en} }