BACKGROUND: Agalsidase β is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase β cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a 'lag time' to clinical benefit after initiating agalsidase β treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase β. METHODS: The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase β (average dose 1 mg/kg every 2 weeks) for up to 5 years. RESULTS: The incidence of all severe clinical events was 111 per 1000 person-years (95% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40-58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged ≥40 years when agalsidase β was initiated. CONCLUSIONS: Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase β 1 mg/kg every 2 weeks. TRIAL REGISTRATION NUMBER: NCT00196742.

Department of Endocrinology and Metabolic Medicine Salford Royal NHS Foundation Trust Salford UK

Department of Genetics São João Hospital Centre and Faculty of Medicine University of Porto Porto Portugal I3S Institute for Research and Innovation in Health University of Porto Porto Portugal

Department of Internal Medicine School of Medicine Charles University Prague Czech Republic

Department of Neurology Fundacion Para el Estudio de Enfermedades Neurometabolicas Buenos Aires Argentina

Department of Pediatrics University of Ulsan College of Medicine Asan Medical Center Seoul Republic of Korea

Departments of Pediatrics and Medicine University of Minnesota Minneapolis Minnesota USA

Division of Cardiovascular Medicine Duke University School of Medicine Durham North Carolina USA

Division of Genetics Birth Defects and Metabolism Ann and Robert H Lurie Children's Hospital of Chicago Chicago Illinois USA Department of Pediatrics Northwestern University Feinberg School of Medicine Chicago Illinois USA

Division of Human Genetics Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA

Division of Medical Genetics University of Versailles St Quentin en Yvelines Versailles France Assistance Publique Hôpitaux de Paris Garches France

Division of Nephrology University Clinic University of Würzburg Würzburg Germany

Division of Nephrology University of Alabama at Birmingham Birmingham Alabama USA

Genzyme a Sanofi Company Cambridge Massachusetts USA

Grupo Medico Del Viso Buenos Aires Argentina

Hôpital du Sacré Coeur de Montréal and University of Montreal Montreal QC Canada

North Ohio Heart Center Westlake Ohio USA

Unidad de Dialisis IIS Fundacion Jimenez Diaz UAM IRSIN Madrid Spain

University of Sunderland Sunderland UK

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Renal and multisystem effectiveness of 3.9 years of migalastat in a global real-world cohort: Results from the followME Fabry Pathfinders registry

Restrictive cardiomyopathy: definition and diagnosis

Prompt Agalsidase Alfa Therapy Initiation is Associated with Improved Renal and Cardiovascular Outcomes in a Fabry Outcome Survey Analysis

The benefits and challenges of family genetic testing in rare genetic diseases-lessons from Fabry disease

Narrative review on Morbus Fabry: diagnosis and management of cardiac manifestations

The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts

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ClinicalTrials.gov
NCT00196742, NCT00196742