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Natural course of Fabry disease and the effectiveness of enzyme replacement therapy: a systematic review and meta-analysis

Effectiveness of ERT in different disease stages

  • Review
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Objective

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.

Design

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.

Data extraction

Two reviewers assessed quality of the included studies according to guidelines for prognosis research. Data were synthesized using a random effects meta-analysis.

Results

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.

Conclusion

ERT is effective in reducing LVH, but has a limited effect on renal function. Improved treatment options are needed for Fabry disease.

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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.

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  1. Department of Internal Medicine, Division of Endocrinology and Metabolism, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands

    Saskia M. Rombach, Bouwien E. Smid, Gabor E. Linthorst & Carla E. M. Hollak

  2. Clinical Research Unit, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands

    Marcel G. W. Dijkgraaf

  3. Department of Internal Medicine/Endocrinology and Metabolism, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Carla E. M. Hollak

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  1. Saskia M. Rombach
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Communicated by: Jean-Marie Saudubray

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Rombach, S.M., Smid, B.E., Linthorst, G.E. et al. Natural course of Fabry disease and the effectiveness of enzyme replacement therapy: a systematic review and meta-analysis. J Inherit Metab Dis 37, 341–352 (2014). https://doi.org/10.1007/s10545-014-9677-8

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