@article {Lenders342, author = {Malte Lenders and Peter Nordbeck and Sima Canaan-K{\"u}hl and Lukas Kreul and Thomas Duning and Lora Lorenz and Christian Pogoda and Stefan-Martin Brand and Christoph Wanner and Eva Brand}, title = {Treatment switch in Fabry disease- a matter of dose?}, volume = {58}, number = {5}, pages = {342--350}, year = {2021}, doi = {10.1136/jmedgenet-2020-106874}, publisher = {BMJ Publishing Group Ltd}, abstract = {Background Patients with Fabry disease (FD) on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in chronic kidney disease epidemiology collaboration-based estimated glomerular filtration rate (eGFR) and a worsened plasma lyso-Gb3 decrease. Hence, the most effective dose is still a matter of debate.Methods In this prospective observational study, we assessed end-organ damage and clinical symptoms in 78 patients who had received agalsidase-beta (1.0 mg/kg) for \>1 year, which were assigned to continue this treatment (agalsidase-beta, regular-dose group, n=17); received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n=22); or were re-switched to agalsidase-beta after receiving agalsidase-alfa for 12 months (re-switch group, n=39) with a follow-up of 88{\textpm}25 months.Results No differences for clinical events were observed for all groups. Patients within the re-switch group started with the worst eGFR values at baseline (p=0.0217). Overall, eGFR values remained stable in the regular-dose group (p=0.1052) and decreased significantly in the re-switch and switch groups (p\<0.0001 and p=0.0052, respectively). However, in all groups males presented with an annual loss of eGFR by {\textendash}2.9, {\textendash}2.5 and -3.9 mL/min/1.73 m{\texttwosuperior} (regular-dose, re-switch, switch groups, all p\<0.05). In females, eGFR decreased significantly only in the re-switch group by -2.9 mL/min/1.73 m{\texttwosuperior} per year (p\<0.01). Lyso-Gb3 decreased in the re-switch group after a change back to agalsidase-beta (p\<0.05).Conclusions Our data suggest that a re-switch to high dosage of agalsidase results in a better biochemical response, but not in a significant renal amelioration especially in classical males.All data relevant to the study are included in the article or uploaded as supplementary information.}, issn = {0022-2593}, URL = {https://jmg.bmj.com/content/58/5/342}, eprint = {https://jmg.bmj.com/content/58/5/342.full.pdf}, journal = {Journal of Medical Genetics} }