TY - JOUR T1 - Treatment switch in Fabry disease- a matter of dose? JF - Journal of Medical Genetics JO - J Med Genet SP - 342 LP - 350 DO - 10.1136/jmedgenet-2020-106874 VL - 58 IS - 5 AU - Malte Lenders AU - Peter Nordbeck AU - Sima Canaan-Kühl AU - Lukas Kreul AU - Thomas Duning AU - Lora Lorenz AU - Christian Pogoda AU - Stefan-Martin Brand AU - Christoph Wanner AU - Eva Brand Y1 - 2021/05/01 UR - http://jmg.bmj.com/content/58/5/342.abstract N2 - 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±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 –2.9, –2.5 and −3.9 mL/min/1.73 m² (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 m² 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. ER -