Dose-dependent impact of ERT on neutralizing anti-drug antibodies and long-term outcomes in Fabry disease

Abstract

Fabry disease (FD) is a rare X-linked disorder caused by a deficiency of lysosomal α-galactosidase A (GLA) activity. Neutralizing anti-drug antibodies (ADA) against enzyme replacement therapy (ERT) are associated with disease progression in male patients. Recently we demonstrated that ADAs can be supersaturated during infusions. In the current work we hypothesized that supersaturated patients benefit from better clinical outcomes. Twenty-six male patients with FD receiving ERT (mean 98±70 months) and positive for ADAs were recruited. Free ADAs were isolated from patients' sera and the amount of ERT necessary for antibody supersaturation was determined. Clinical outcomes including measurements of eGFR and septum thickness of supersaturated patients were compared to non-supersaturated patients. ADA titers decreased in all patients (n=26) during infusion (p