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

Molecular Genetics and Metabolism Reports. 2019;19


Journal Homepage

Journal Title: Molecular Genetics and Metabolism Reports

ISSN: 2214-4269 (Online)

Publisher: Elsevier

LCC Subject Category: Medicine: Medicine (General) | Science: Biology (General)

Country of publisher: United States

Language of fulltext: English

Full-text formats available: PDF, HTML



Dominique P. Germain (French Referral Center for Fabry disease, Division of Medical Genetics and INSERM U1179, University of Versailles, Paris-Saclay University, Montigny, France; Corresponding author.)

Perry M. Elliott (University College London and Barts Heart Centre, London, United Kingdom)

Bruno Falissard (INSERM U1018, University of Paris-Sud, University of Paris-Descartes, Paris, France)

Victor V. Fomin (Department of Internal Diseases No.1, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation)

Max J. Hilz (Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany)

Ana Jovanovic (Mark Holland Metabolic Unit, Salford Royal NHS Foundation Trust, Salford, United Kingdom)

Ilkka Kantola (Division of Medicine, Turku University Hospital, University of Turku, Turku, Finland)

Aleš Linhart (Second Department of Medicine – Department of Cardiovascular Medicine, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic)

Renzo Mignani (Department of Nephrology, Infermi Hospital, Rimini, Italy)

Mehdi Namdar (Service de Cardiologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland)

Albina Nowak (Department of Internal Medicine, University Hospital of Zurich and University of Zurich, Zurich, Switzerland)

João-Paulo Oliveira (Department of Genetics, São João Hospital Centre and Faculty of Medicine and “Instituto de Investigação e Inovação em Saúde (iS3)”, University of Porto, Porto, Portugal)

Maurizio Pieroni (Cardiovascular Department, San Donato Hospital, Arezzo, Italy)

Miguel Viana-Baptista (Serviço de Neurologia, Hospital Egas Moniz, Centro Hospitalar de Lisboa Ocidental; CEDOC Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal)

Christoph Wanner (Division of Nephrology, University Clinic, University of Würzburg, Würzburg, Germany)

Marco Spada (Department of Paediatrics, University of Torino, Torino, Italy)


Peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 8 weeks


Abstract | Full Text

Background: Enzyme replacement therapy (ERT) with recombinant human α-galactosidase has been available for the treatment of Fabry disease since 2001 in Europe and 2003 in the USA. Treatment outcomes with ERT are dependent on baseline patient characteristics, and published data are derived from heterogeneous study populations. Methods: We conducted a comprehensive systematic literature review of all original articles on ERT in the treatment of Fabry disease published up until January 2017. This article presents the findings in adult male patients. Results: Clinical evidence for the efficacy of ERT in adult male patients was available from 166 publications including 36 clinical trial publications. ERT significantly decreases globotriaosylceramide levels in plasma, urine, and in different kidney, heart, and skin cell types, slows the decline in estimated glomerular filtration rate, and reduces/stabilizes left ventricular mass and cardiac wall thickness. ERT also improves nervous system, gastrointestinal, pain, and quality of life outcomes. Conclusions: ERT is a disease-specific treatment for patients with Fabry disease that may provide clinical benefits on several outcomes and organ systems. Better outcomes may be observed when treatment is started at an early age prior to the development of organ damage such as chronic kidney disease or cardiac fibrosis. Consolidated evidence suggests a dose effect. Data described in male patients, together with female and paediatric data, informs clinical practice and therapeutic goals for individualized treatment. Keywords: Fabry disease, agalsidase alfa, agalsidase beta, systematic literature review, enzyme replacement therapy, adult male patients