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: ACEi, angiotensin-converting enzyme inhibitor; ANS, autonomic nervous system; ARB, angiotensin receptor blocker; BPI, Brief Pain Inventory; CES-D, Center for Epidemiologic Studies Depression Scale; CNS, central nervous system; CR, case report; CT, clinical trial; ECG, electrocardiogram/electrocardiography; EOW, every other week; ERT, enzyme replacement therapy; Fabry disease; GFR, glomerular filtration rate; GI, gastrointestinal; GL-3, globotriaosylceramide; IENFD, intra-epidermal nerve fibre density; IVST, intraventricular septum thickness; LPWT, left posterior wall thickness; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; LVM, left ventricular mass; LVMi, left ventricular mass index; LVWT, left ventricular wall thickness; MG, mixed gender; MRI, magnetic resonance imaging; MWT, maximal wall thickness; NYHA, New York Heart Association; OS, observational study; PNS, peripheral nervous system; QoL, quality of life; RCT, randomized controlled trial; SF-36, 36-item Short Form Health Survey; TIA, transient ischaemic attack; WMH, white matter hyperintensities.; adult male patients; agalsidase alfa; agalsidase beta; eGFR, estimated glomerular filtration rate; enzyme replacement therapy; lyso-GL-3, globotriaosylsphingosine; systematic literature review.