Fabry 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.

Department of Cardiovascular Medicine 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Medicine Universidad Autónoma de Madrid Madrid Spain

Department of Public Health University of Naples Federico 2 Naples Italy

Division of Medicine Turku University Hospital Turku University Turku Finland

General University Hospital Prague Czech Republic

Jiménez Díaz Foundation University Hospital and IIS Fundación Jiménez Díaz UAM Madrid Spain

Navitas Data Sciences Pottstown Pennsylvania USA

Neurology Department Fundación SPINE Buenos Aires Argentina

Sanofi Cambridge Massachusetts USA

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Lysosomal Storage-Independent Fabry Disease Variants with α-Galactosidase A Misprocessing-Induced ER Stress and the Unfolded Protein Response