Abstract
The treatment options for Fabry disease (FD) are enzyme replacement therapy (ERT) with agalsidase alfa or beta, and the oral pharmacological chaperone migalastat. Since few data are available on the effects of switching from ERT to migalastat, we performed a single-center observational study on seven male Fabry patients (18–66 years) to assess the effects of the switch on renal, cardiac, and neurologic function, health status, pain, lyso-Gb3, α-Gal A activity and adverse effects. Data were retrospectively collected at time of diagnosis of FD (baseline, T0), and after 12 months of ERT (T1), and prospectively after 1 year of therapy with migalastat (T2). No patient died or reported renal, cardiac, or cerebrovascular events during the study period. The predefined measures for cardiac, renal and neurologic function, and FD-related symptoms and questionnaires were stable between baseline and the switch, and remained unchanged with migalastat. However, a significant improvement was observed in left ventricular mass index from baseline to T2 (p = 0.016), with a significative difference between the treatments (p = 0.028), and in median proteinuria from T2 vs T1 (p = 0.048). Moreover, scores of the BPI improved from baseline to T1, and remained stable with migalastat. Plasma lyso-Gb3 levels significantly decreased from baseline to T1 (P = 0.007) and T2 (P = 0.003), while did not significantly differ between the two treatments. α-Gal A activity increased from T0 to T2 (p < 0.0001). The frequency of adverse effects under migalastat and ERT was comparable (28% for both drugs). In conclusion, switching from ERT to migalastat is valid, safe and well tolerated.
Highlights
Fabry disease (FD) is an X-linked disorder caused by lysosomal α-galactosidase A (α-Gal) deficiency, with subsequent deposition of undegraded glycosphingolipid products, mainly globotriaosylceramide (Gb3) and Members of the AFFIINITY Group Consortium are listed in end of paper
As an orally administered small-molecule agent, migalastat may obviate the burden of life-long administration of enzyme replacement therapy (ERT) every 2 weeks
The pharmacological kinetics of the migalastat and its reversible bond with the α-galactosidase in vivo should be taken into consideration when we refer to the biological activity of migalastat [23]
Summary
University of Naples, Naples, Italy 4 Nephrology and Dialysis Department, Belcolle Hospital, Viterbo, Italy globotriaosylsphingosine (lyso-Gb3), in multiple organs, with significant morbidity and premature death [1]. The treatment options for this genetic disease were limited to enzyme replacement therapy (ERT) with agalsidase alfa or beta. It reversibly binds to the active site and stabilizes specific mutant forms of α-Gal, defined “amenable” to migalastat, promoving trafficking to lysosomes, where it allows the enzyme to catabolize accumulated substrates [8,9,10,11].
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