Natural course of Fabry disease and the effectiveness of enzyme replacement therapy: a systematic review and meta-analysis
- 2.1k Downloads
Current available evidence on long-term effectiveness of enzyme replacement therapy (ERT) for Fabry disease is limited. More insight is needed whether ERT effectiveness differs in patients with and without baseline end-organ damage.
Through a systematic review, untreated and ERT treated males and females with Fabry disease were compared for main clinical outcomes: renal function, left ventricular mass (LVmass), cerebral white matter lesions (WMLs) and end-organ complications. Through a meta-analysis ERT effectiveness was estimated in different disease stages.
Two reviewers assessed quality of the included studies according to guidelines for prognosis research. Data were synthesized using a random effects meta-analysis.
Thirty-one studies were systematically reviewed while six studies were included in the meta-analysis. In patients with a GFR > 60 ml/min/1.73 m2, decline of renal function was similar for treated and untreated patients. Only ERT treated males with a GFR < 60 ml/min/1.73 m2 had a slower rate of decline in renal function, possibly attributable to anti-proteinuric therapy. Regardless of left ventricular hypertrophy (LVH) at baseline, LVmass remained stable or increased in males despite ERT, however at a slower rate compared to untreated male patients. In ERT treated females with LVH LVmass decreased, and remained stable in females without LVH. WMLs can not be prevented by ERT. Stroke, cardiac and end-stage renal complications develop, though the incidence of new complications seems to be reduced during ERT.
ERT is effective in reducing LVH, but has a limited effect on renal function. Improved treatment options are needed for Fabry disease.
KeywordsRenal Function Glomerular Filtration Rate Left Ventricular Hypertrophy Enzyme Replacement Therapy Fabry Disease
Conflict of Interest
S.M. Rombach, B.E. Smid and M.G.W. Dijkgraaf declare that they have no competing interests.
C.E.M. Hollak received reimbursement of expenses and honoraria for lectures on the management of lysosomal storage diseases from Genzyme Corporation, Shire, Actelion and Amicus Therapeutics and Protalix. All honoraria are donated to the Gaucher Stichting OR AMC Research BV, a national foundation that supports research in the field of lysosomal storage disorders.
G.E. Linthorst received reimbursement of expenses and honoraria for lectures on the management of lysosomal storage diseases from Genzyme Corporation, Shire, Actelion and Amicus Therapeutics and Protalix. All honoraria are donated to the Gaucher Stichting OR AMC Research BV, a national foundation that supports research in the field of lysosomal storage disorders.
- Desnick RJ, Ioannou YA, Eng CM (2001) alpha-Galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, vol 3, 8th edn., pp 3733–3774Google Scholar
- El Dib RP, Pastores GM (2010) Enzyme replacement therapy for Anderson-Fabry disease. Cochrane Database Syst Rev CD006663Google Scholar
- Engelen MA, Brand E, Baumeister TB et al (2012) Effects of enzyme replacement therapy in adult patients with Fabry disease on cardiac structure and function: a retrospective cohort study of the Fabry Munster Study (FaMuS) data. BMJ Open 2Google Scholar
- Hughes DA, Barba Romero MA, Hollak CE, Giugliani R, Deegan PB (2011) Response of women with Fabry disease to enzyme replacement therapy: comparison with men, using data from FOS-the Fabry Outcome Survey. Mol Genet Metab 103(3):207-14. doi: 10.1016/j.ymgme.2011.03.022 Google Scholar
- Kobayashi M, OhashiT, Sakuma M, Ida H, EtoY (2008) Clinical manifestations and natural history of Japanese heterozygous females with Fabry disease. J Inherit Metab Dis doi:10.1007/s10545-007-0740-6Google Scholar
- Schiffmann R, Martin RA, Reimschisel T et al (2010) Four-year prospective clinical trial of agalsidase alfa in children with Fabry disease. J Pediatr 156(832–7):837Google Scholar
- Wanner C, Oliveira JP, Ortiz A et al (2010) Prognostic indicators of renal disease progression in adults with Fabry disease: natural history data from the Fabry registry. Clin J Am Soc Nephrol 5(12):2220-8. doi: 10.2215/CJN.04340510Google Scholar
- Warnock DG, Ortiz A, Mauer M et al (2011) Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation. Nephrol Dial Transplant 27(3):1042-9. doi: 10.1093/ndt/gfr420Google Scholar
- Weidemann F, Niemann M, Stork S et al (2013) Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications. J Intern Med 274(4):331-41. doi: 10.1111/joim.12077 Google Scholar
- Wraith JE, Tylki-Szymanska A et al (2008) Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease. J Pediatr 152(563–70):570Google Scholar