The value of registries in the study of rare diseases: Fabry Outcome Survey

Abstract

Randomized controlled clinical trials are frequently hardly feasible in patients with orphan disorders given the limited number of potential participants and variablity of clinical manifestations and the course of disease. Registry data, particularly for rare diseases, provide additional information regarding long-term treatment effectiveness and safety. The year 2021 marked the 20th anniversary of the Fabry Outcome Survey (FOS), an international, multicenter, observational registry (NCT03289065). The aim of FOS was to study Fabry disease, an X-linked lysosomal storage disorder caused by mutations in the galactosidase alpha (GLA) gene that result in reduced or absent a-galactosidase A activity and sphyngolipids accumulation in the various tissues. As of January 2021, 4484 patients with Fabry disease have been enrolled in FOS from 144 centers across 26 countries. Analyses of FOS data has confirmed the efficacy and safety of enzyme replacement therapy with agalsidase alfa and its favorable impact on the course of Fabry disease and mortality. FOS data have also shown the advantages of prompt treatment that was more effective in prevention of cardiovascular and renal events regardless of type of disease.