@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} } @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{GermainAradBurlinaetal.2019, author = {Germain, Dominique P. and Arad, Michael and Burlina, Alessandro and Elliott, Perry M. and Falissard, Bruno and Feldt-Rasmussen, Ulla and Hilz, Max J. and Hughes, Derralynn A. and Ortiz, Alberto and Wanner, Christoph and Weidemann, Frank and Spada, Marco}, title = {The effect of enzyme replacement therapy on clinical outcomes in female patients with Fabry disease - A systematic literature review by a European panel of experts}, series = {Molecular Genetics and Metabolism}, volume = {126}, journal = {Molecular Genetics and Metabolism}, doi = {10.1016/j.ymgme.2018.09.007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232963}, pages = {224-235}, year = {2019}, abstract = {Background Heterozygous females with Fabry disease have a wide range of clinical phenotypes depending on the nature of their mutation and their X-chromosome inactivation pattern; it is therefore important to examine outcomes of enzyme replacement therapy (ERT) in the female patient population specifically. This paper presents the findings of a systematic literature review of treatment outcomes with ERT in adult female patients. Methods A comprehensive systematic literature review was conducted through January 2017 to retrieve published papers with original data on ERT in the treatment of Fabry disease. The review included all original articles that presented ERT outcomes data on patients with Fabry disease, irrespective of the study type. Results Clinical evidence for the efficacy of ERT in female patients was available from 67 publications including six clinical trial publications, and indicates significant reductions in plasma and urine globotriaosylceramide (GL-3) accumulation (in female patients with elevated pre-treatment levels) and improvements in cardiac parameters and quality of life (QoL). To date, data are insufficient to conclude on the effects of ERT on the nervous system, gastrointestinal manifestations, and pain in female patients with Fabry disease. Conclusions This review of available literature data demonstrates that ERT in adult female patients with Fabry disease has a beneficial effect on GL-3 levels and cardiac outcomes. The current evidence also suggests that ERT may improve QoL in this patient population, though further studies are needed to examine these results.}, language = {en} } @article{GermainBrandBurlinaetal.2018, author = {Germain, Dominique P. and Brand, Eva and Burlina, Alessandro and Cecchi, Franco and Garman, Scott C. and Kempf, Judy and Laney, Dawn A. and Linhart, Aleš and Mar{\´o}di, L{\´a}szl{\´o} and Nicholls, Kathy and Ortiz, Alberto and Pieruzzi, Federico and Shankar, Suma P. and Waldek, Stephen and Wanner, Christoph and Jovanovic, Ana}, title = {Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease: A multicenter Fabry Registry study}, series = {Molecular Genetics \& Genomic Medicine}, volume = {6}, journal = {Molecular Genetics \& Genomic Medicine}, doi = {10.1002/mgg3.389}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232976}, pages = {492-503}, year = {2018}, abstract = {Background The p.Asn215Ser or p.N215S GLA variant has been associated with late-onset cardiac variant of Fabry disease. Methods To expand on the scarce phenotype data, we analyzed natural history data from 125 p.N215S patients (66 females, 59 males) enrolled in the Fabry Registry (NCT00196742) and compared it with data from 401 patients (237 females, 164 males) harboring mutations associated with classic Fabry disease. We evaluated interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), estimated glomerular filtration rate and severe clinical events. Results In p.N215S males, mildly abnormal mean IVST and LVPWT values were observed in patients aged 25-34 years, and values gradually increased with advancing age. Mean values were similar to those of classic males. In p.N215S females, these abnormalities occurred primarily in patients aged 55-64 years. Severe clinical events in p.N215S patients were mainly cardiac (males 31\%, females 8\%) while renal and cerebrovascular events were rare. Renal impairment occurred in 17\% of p.N215S males (mostly in patients aged 65-74 years), and rarely in females (3\%). Conclusion p.N215S is a disease-causing mutation with severe clinical manifestations found primarily in the heart. Cardiac involvement may become as severe as in classic Fabry patients, especially in males.}, language = {en} } @article{LevitisGouldvan PraagGauetal.2021, author = {Levitis, Elizabeth and Gould van Praag, Cassandra D and Gau, R{\´e}mi and Heunis, Stephan and DuPre, Elizabeth and Kiar, Gregory and Bottenhorn, Katherine L and Glatard, Tristan and Nikolaidis, Aki and Whitaker, Kirstie Jane and Mancini, Matteo and Niso, Guiomar and Afyouni, Soroosh and Alonso-Ortiz, Eva and Appelhoff, Stefan and Arnatkeviciute, Aurina and Atay, Selim Melvin and Auer, Tibor and Baracchini, Giulia and Bayer, Johanna M M and Beauvais, Michael J S and Bijsterbosch, Janine D and Bilgin, Isil P and Bollmann, Saskia and Bollmann, Steffen and Botvinik-Nezer, Rotem and Bright, Molly G and Calhoun, Vince D and Chen, Xiao and Chopra, Sidhant and Chuan-Peng, Hu and Close, Thomas G and Cookson, Savannah L and Craddock, R Cameron and De La Vega, Alejandro and De Leener, Benjamin and Demeter, Damion V and Di Maio, Paola and Dickie, Erin W and Eickhoff, Simon B and Esteban, Oscar and Finc, Karolina and Frigo, Matteo and Ganesan, Saampras and Ganz, Melanie and Garner, Kelly G and Garza-Villarreal, Eduardo A and Gonzalez-Escamilla, Gabriel and Goswami, Rohit and Griffiths, John D and Grootswagers, Tijl and Guay, Samuel and Guest, Olivia and Handwerker, Daniel A and Herholz, Peer and Heuer, Katja and Huijser, Dorien C and Iacovella, Vittorio and Joseph, Michael J E and Karakuzu, Agah and Keator, David B and Kobeleva, Xenia and Kumar, Manoj and Laird, Angela R and Larson-Prior, Linda J and Lautarescu, Alexandra and Lazari, Alberto and Legarreta, Jon Haitz and Li, Xue-Ying and Lv, Jinglei and Mansour L., Sina and Meunier, David and Moraczewski, Dustin and Nandi, Tulika and Nastase, Samuel A and Nau, Matthias and Noble, Stephanie and Norgaard, Martin and Obungoloch, Johnes and Oostenveld, Robert and Orchard, Edwina R and Pinho, Ana Lu{\´i}sa and Poldrack, Russell A and Qiu, Anqi and Raamana, Pradeep Reddy and Rokem, Ariel and Rutherford, Saige and Sharan, Malvika and Shaw, Thomas B and Syeda, Warda T and Testerman, Meghan M and Toro, Roberto and Valk, Sofie L and Van Den Bossche, Sofie and Varoquaux, Ga{\"e}l and V{\´a}ša, František and Veldsman, Michele and Vohryzek, Jakub and Wagner, Adina S and Walsh, Reubs J and White, Tonya and Wong, Fu-Te and Xie, Xihe and Yan, Chao-Gan and Yang, Yu-Fang and Yee, Yohan and Zanitti, Gaston E and Van Gulick, Ana E and Duff, Eugene and Maumet, Camille}, title = {Centering inclusivity in the design of online conferences—An OHBM-Open Science perspective}, series = {GigaScience}, volume = {10}, journal = {GigaScience}, doi = {10.1093/gigascience/giab051}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-371574}, pages = {1-14}, year = {2021}, abstract = {As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities. Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements of an online conference are still significant barriers to truly diverse participation: the tools used can be inaccessible for some individuals; the scheduling choices can favour some geographical locations; the set-up of the conference can provide more visibility to well-established researchers and reduce opportunities for early-career researchers. While acknowledging the benefits of an online setting, especially for individuals who have traditionally been underrepresented or excluded, we recognize that fostering social justice requires inclusivity to actively be centered in every aspect of online conference design. Here, we draw from the literature and from our own experiences to identify practices that purposefully encourage a diverse community to attend, participate in, and lead online conferences. Reflecting on how to design more inclusive online events is especially important as multiple scientific organizations have announced that they will continue offering an online version of their event when in-person conferences can resume.}, language = {en} }