Favourable effect of early versus late start of enzyme replacement therapy on plasma globotriaosylsphingosine levels in men with classical Fabry disease

Background: The level of plasma globotriaosylsphingosine (lysoGb3) is an indication of disease severity in Fabry disease (FD) and its decrease during enzyme replacement therapy could be a reflection of treatment efficacy. Early treatment of FD may improve clinical outcome, but data to support this hypothesis are scarce. In this study we compared lysoGb3 decrease after ERT initiation in men with classical FD who started ERT before the age of 25 (early-treatment) with those who started later in life (late-treatment). Methods: Treatment naive men with classical FD from three centers of excellence in Europe were included. Measurements of lysoGb3 levels by tandem mass spectroscopy and antibodies by an inhibitory assay were performed in a single laboratory. Results were adjusted for lysoGb3 at baseline, first ERT (i.e. agalsidase alfa or beta) and the average ERT dose. Results: 85 patients were included, 21 in the early-treatment and 64 in the late-treatment group. LysoGb3 level at baseline was not different between the two groups (112 vs 114 nmol/L, p = 0.92). The adjusted odds ratio for reaching a lysoGb3 level <20 nmol/L was 7.38 for the early-treatment versus late-treatment group (95% CI: 1.91-34.04, p = 0.006). The adjusted lysoGb3 levels one year after ERT initiation was 12.9 nmol/L lower in the early-treatment (95% CI: -20.1--5.8, p <0.001) compared to the late-treatment group. Conclusion: The current retrospective cohort study shows that initiation of ERT at younger age in men with classical Fabry disease results in a better biochemical response. (C) 2017 Elsevier Inc. All rights reserved