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

Mol Genet Metab Rep. 2019 Feb 6;19:100454. doi:10.1016/j.ymgmr.2019.100454. eCollection 2019 Jun.

PMID: 30775256

Dominique P Germain, Perry M Elliott, Bruno Falissard, Victor V Fomin, Max J Hilz, Ana Jovanovic, Ilkka Kantola, Aleš Linhart, Renzo Mignani, Mehdi Namdar, Albina Nowak, João-Paulo Oliveira, Maurizio Pieroni, Miguel Viana-Baptista, Christoph Wanner, Marco Spada

Summary: This article is a systematic review that includes 166 publications about enzyme replacement therapy (ERT) in the treatment of Fabry disease. When treatment is initiated early, better outcomes may be observed. There is a dose effect, according to the evidence. When data described in male patients, together with female and paediatric data, are evaluated, these inform clinical practice and therapeutic goals for individualized treatment.

Abstract

Background: Since 2001 in Europe and 2003 in the United States, enzyme replacement therapy (ERT) with recombinant human-galactosidase has been available for the treatment of Fabry disease. Treatment outcomes with ERT are influenced by patient characteristics from the outset, and published data comes from a variety of study populations.

Methods: A systematic review was conducted of all original studies on ERT in the treatment of Fabry disease that had been published up until January 2017. The findings of adult male patients are presented in this article.

Results: 166 publications, including 36 clinical trial papers, provided clinical evidence supporting the efficacy of ERT in adult male patients. ERT lowers globotriaosylceramide levels in plasma, urine, and various kidney, heart, and skin cell types, slows the reduction in estimated glomerular filtration rate and reduces/stabilizes left ventricular mass and cardiac wall thickness. It also. ERT also helps to improve the neurological symptoms, gastrointestinal issues, discomfort, and overall quality of life.

Conclusions: ERT is a disease-specific treatment for Fabry disease patients that may improve a variety of clinical outcomes and organ systems. When treatment is initiated at a young age, before organ damage such as chronic renal disease or cardiac fibrosis develops, better outcomes may be observed. There is a dose effect, according to the consolidated evidence. When data described in male patients, together with female and paediatric data, are evaluated, these inform clinical practice and therapeutic goals for individualized treatment.

Keywords: ERT, enzyme replacement therapy; Fabry disease; GL-3, globotriaosylceramide; OS, observational study; QoL, quality of life; RCT, randomized controlled trial; adult male patients; agalsidase alfa; agalsidase beta; lyso-GL-3, globotriaosylsphingosine; systematic literature review.