@article{WannerFeldtRasmussenJovanovicetal.2020,
  author    = {Wanner, Christoph and Feldt-Rasmussen, Ulla and Jovanovic, Ana and Linhart, Aleš and Yang, Meng and Ponce, Elvira and Brand, Eva and Germain, Dominique P. and Hughes, Derralynn A. and Jefferies, John L. and Martins, Anna Maria and Nowak, Albina and Vujkovac, Bojan and Weidemann, Frank and West, Michael L. and Ortiz, Alberto},
  title     = {Cardiomyopathy and kidney function in agalsidase beta-treated female Fabry patients: a pre-treatment vs. post-treatment analysis},
  series = {ESC Heart Failure},
  volume    = {7},
  journal   = {ESC Heart Failure},
  number    = {3},
  doi       = {10.1002/ehf2.12647},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235963},
  pages     = {825-834},
  year      = {2020},
  abstract  = {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.},
  language  = {en}
}
@article{OrtizAbioseBichetetal.2016,
  author    = {Ortiz, Alberto and Abiose, Ademola and Bichet, Daniel G. and Cabrera, Gustavo and Charrow, Joel and Germain, Dominique P. and Hopkin, Robert J. and Jovanovic, Ana and Linhart, Aleš and Maruti, Sonia S. and Mauer, Michael and Oliveira, Jo{\~a}o P. and Patel, Manesh R. and Politei, Juan and Waldek, Stephen and Wanner, Christoph and Yoo, Han-Wook and Warnock, David G.},
  title     = {Time to treatment benefit for adult patients with Fabry disease receiving agalsidase beta: data from the Fabry Registry},
  series = {Journal of Medical Genetics},
  volume    = {53},
  journal   = {Journal of Medical Genetics},
  number    = {7},
  doi       = {10.1136/jmedgenet-2015-103486},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188241},
  pages     = {495-502},
  year      = {2016},
  abstract  = {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.},
  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}
}