Elsevier

Clinical Therapeutics

Volume 31, Issue 9, September 2009, Pages 1966-1976
Clinical Therapeutics

Effect of agalsidase alfa replacement therapy on fabry disease—related hypertrophic cardiomyopathy: A 12- to 36-month, retrospective, blinded echocardiographic pooled analysis

https://doi.org/10.1016/j.clinthera.2009.09.008Get rights and content

Abstract

Background: Fabry disease is an X-linked disease caused by a deficiency in the activity of the lysosomal enzyme α-galactosidase A. Affected individuals typically develop left ventricular hypertrophy (LVH) among other pathologies.

Objective: The purpose of the present study was to investigate the effect of ≥12 months of enzyme replacement therapy (ERT) with agalsidase alfa on LV mass (LVM) in men and women with Fabry disease.

Methods: This was a retrospective, blinded, pooled analysis of data from several studies assessing the effect of ERT with agalsidase alfa on LVM in patients with Fabry disease with baseline LVH. Men and women aged ≥18 years with a confirmed diagnosis of Fabry disease who had received ≥36 months of ERT with agalsidase alfa were eligible, provided they had a baseline echocardiogram and a follow-up echocardiogram at 12 and/or 36 months. Data from 4 studies were included in the present analysis. LVM was normalized to height (in meters) to the 2.7 power (LVM/h = LVM/m2.7).

Results: In total, 45 adult patients (34 men and 11 women) with a confirmed diagnosis of Fabry disease and serial echocardiograms obtained at baseline and after 12 and/or 36 months of treatment were included. The mean (SD) age of this cohort was 39.8 (10.4) years (range, 18.9–67.2 years), and the mean weight was 72.5 (13.4) kg (range, 46.7–102.9 kg). Forty-two patients were white, 2 were Hispanic, and 1 was classified as other. At baseline, 14 patients had LVH (mean LVM/h = 55.4 [5.7] g/m2.7). After 12 months of ERT with agalsidase alfa, LVM/h decreased significantly by 9.2 (7.9) g/m2.7 in 9 patients (P = 0.008), and after 36 months, LVM/h decreased significantly by 5.1 (7.5) g/m2.7 in 10 patients (P = 0.037). In patients without baseline LVH (n = 31), a significant increase in LVM/h was observed after 12 months of treatment (3.6 [5.7] g/m2.7; P = 0.002). After 36 months of treatment, however, there was no significant change from baseline in 10 patients (2.1 [7.9] g/m2.7; P = NS).

Conclusion: Treatment with agalsidase alfa for 12 or 36 months was associated with reduced LVM in these patients with Fabry disease with baseline LVH, and it appeared to stabilize LVM in these patients without baseline LVH.

References (45)

  • AC Vedder et al.

    Treatment of Fabry disease with different dosing regimens of agalsidase: Effects on antibody formation and GL-3

    Mol Genet Metab.

    (2008)
  • M Elleder et al.

    Cardiocyte storage and hypertrophy as a sole manifestation of Fabry's disease. Report on a case simulating hypertrophic non-obstructive cardiomyopathy

    Virchows Arch A Pathol Anat Histopathol.

    (1990)
  • M Uchino et al.

    A histochemical and electron microscopic study of skeletal and cardiac muscle from a Fabry disease patient and carrier

    Acta Neuropathol.

    (1995)
  • RO Brady et al.

    Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency

    N Engl J Med.

    (1967)
  • PJ Meikle et al.

    Prevalence of lysosomal storage disorders

    JAMA

    (1999)
  • KD MacDermot et al.

    Anderson-Fabry disease: Clinical manifestations and impact of disease in a cohort of 98 hemizygous males

    J Med Genet.

    (2001)
  • KD MacDermot et al.

    Anderson-Fabry disease: Clinical manifestations and impact of disease in a cohort of 60 obligate carrier females

    J Med Genet.

    (2001)
  • A Linhart et al.

    Cardiac manifestations of Anderson-Fabry disease: Results from the international Fabry Outcome Survey

    Eur Heart J.

    (2007)
  • JS Shah et al.

    Fabry disease and the heart: An overview of the natural history and the effect of enzyme replacement therapy

    Acta Paediatr Suppl.

    (2005)
    JS Shah et al.

    Fabry disease and the heart: An overview of the natural history and the effect of enzyme replacement therapy

    Acta Paediatr Suppl.

    (2005)
  • Schiffmann R, Warnock DG, Banikazemi M, et al. Fabry disease: Progression of nephropathy, and prevalence of cardiac and...
  • C Kampmann et al.

    The heart in Anderson Fabry disease

    Z Kardiol.

    (2002)
  • H Hasegawa et al.

    Images in cardiovascular medicine. Transition from left ventricular hypertrophy to massive fibrosis in the cardiac variant of Fabry disease

    Circulation

    (2006)
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    Currently affiliated with the Baylor Institute of Metabolic Disease, Dallas, Texas.

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