AIMS: Long-term treatment effect studies in large female Fabry patient groups are challenging to design because of phenotype heterogeneity and lack of appropriate comparison groups, and have not been reported. We compared long-term cardiomyopathy and kidney function outcomes after agalsidase beta treatment with preceding treatment-naive outcomes. METHODS AND RESULTS: Self-controlled pretreatment and post-treatment comparison (piecewise mixed linear modelling) included Fabry female patients ≥18 years at treatment initiation who received agalsidase beta (0.9-1.1 mg/kg every other week) for ≥2 years, with ≥2 pretreatment and ≥2 post-treatment outcome measurements during 10-year follow-up. Left ventricular posterior wall thickness (LVPWT)/interventricular septal thickness (IVST) and estimated glomerular filtration rate (eGFR, Chronic Kidney Disease Epidemiology Collaboration creatinine equation) analyses included 42 and 86 patients, respectively, aged 50.0 and 46.3 years at treatment initiation, respectively. LVPWT and IVST increased pretreatment (follow-up 3.5 years) but stabilized during 3.6 years of treatment (LVPWT: n = 38, slope difference [95% confidence interval (CI)] = -0.41 [-0.68, -0.15] mm/year, Ppre-post difference <0.01; IVST: n = 38, slope difference = -0.32 [-0.67, 0.02] mm/year, Ppre-post difference = 0.07). These findings were not modified by renal involvement or antiproteinuric agent use. Compared with the treatment-naive period (follow-up 3.6 years), eGFR decline remained modest and stabilized within normal ranges during 4.1 years of treatment (slope difference, 95% CI: -0.13 [-1.15, 0.89] mL/min/1.73m2 /year, Ppre-post difference = 0.80). CONCLUSIONS: Cardiac hypertrophy, progressing during pretreatment follow-up, appeared to stabilize during sustained agalsidase beta treatment. eGFR decline remained within normal ranges. This suggests that treatment may prevent further Fabry-related progression of cardiomyopathy in female patients and maintain normal kidney function.

2nd Department of Medicine Department of Cardiovascular Medicine 1st Faculty of Medicine Charles University General University Hospital Prague Czech Republic

Department of Internal Medicine General Hospital Slovenj Gradec Slovenj Gradec Slovenia

Department of Internal Medicine University Hospital of Zürich University of Zürich Zürich Switzerland

Department of Medical Endocrinology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Medicine Division of Cardiovascular Diseases University of Tennessee Health Science Center Memphis TN USA

Department of Medicine Division of Nephrology Dalhousie University Halifax Nova Scotia Canada

Department of Medicine Division of Nephrology University Hospital Würzburg Würzburg Germany

Department of Paediatrics Federal University of São Paulo São Paulo Brazil

Epidemiology and Biostatistics Sanofi Genzyme Cambridge MA USA

French Referral Center for Fabry Disease Division of Medical Genetics and INSERM U1179 University of Versailles Paris Saclay University Montigny France

Global Medical Affairs Rare Diseases Sanofi Genzyme Cambridge MA USA

Internal Medicine D Department of Nephrology Hypertension and Rheumatology University Hospital Münster Münster Germany

Lysosomal Storage Disorder Unit Royal Free London NHS Foundation Trust and University College London London UK

Medical Clinic 1 Klinikum Vest Knappschaftskrankenhaus Recklinghausen Germany

The Mark Holland Unit Department of Endocrinology and Metabolic Medicine Salford Royal NHS Foundation Trust Salford UK

Unidad de Dialisis IIS Fundación Jiménez Díaz UAM IRSIN REDINREN Madrid Spain

Future Cardiol. 2022 Sep;18(10):755-763. doi: 10.2217/fca-2022-0047. PubMed

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