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

- Baseline lysoGb3 values of early-treated (< 25 years of age) and late-treated (≥ 25 years of age) classical FD men are similar.
- LysoGb3 reduction following enzyme replacement therapy is more pronounced in the early-treatment group.
- Even at young age a significant proportion of the patients already showed signs of organ involvement.

BackgroundThe 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).MethodsTreatment naïve 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.Results85 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.ConclusionThe current retrospective cohort study shows that initiation of ERT at younger age in men with classical Fabry disease results in a better biochemical response.