Clinical outcomes in patients switching from agalsidase beta to migalastat: A Fabry Registry analysis

Abstract

AbstractFabry Registry data were analyzed among 83 agalsidase beta‐treated patients with Fabry disease who switched to migalastat. Outcomes (estimated glomerular filtration rate [eGFR], urine protein‐creatinine ratio [UPCR], plasma globotriaosylceramide [GL‐3], plasma globotriaosylsphingosine [lyso‐GL‐3], interventricular septal wall thickness [IVST], left posterior wall thickness [LPWT], left ventricular mass index [LVMI]) were assessed using linear mixed models to estimate annual change over time in the pre‐ and postswitch periods. eGFR decreased throughout both periods (preswitch: −0.85 mL/min/1.73 m2/year; postswitch: −1.96 mL/min/1.73 m2/year; both p < 0.0001), with steeper decline postswitch (ppre/post = 0.01) in both classic and late‐onset patients. UPCR increased significantly postswitch (ppre/post = 0.003) among classic patients and was stable in both periods among late‐onset patients. GL‐3 trajectories worsened postswitch across phenotypes (ppre/post = 0.0005 classic, 0.02 late‐onset). LPWT was stable preswitch (0.07 mm/year, p = 0.25) and decreased postswitch (−0.51 mm/year, p = 0.0005; ppre/post = 0.0009), primarily among late‐onset patients. IVST and LVMI slopes varied significantly by phenotype. Among classic patients, IVST and LVMI were stable and decreasing, respectively preswitch and increasing postswitch (ppre/post = 0.02 IVST, 0.01 LVMI). Among late‐onset patients, IVST significantly decreased postswitch (ppre/post = 0.0003); LVMI was stable over time (ppre/post = 0.89). Ultimately, eGFR and GL‐3 trajectories worsened postswitch across phenotypes, while UPCR and cardiac measures worsened among classic and stabilized/improved among late‐onset patients. These findings indicate variability in long‐term outcomes after switching from ERT to migalastat, underscoring the importance of careful monitoring.