Enzyme replacement therapy for Fabry disease: A systematic review and meta-analysis

Abstract

The specific treatment available for Fabry disease (FD) is enzyme replacement therapy (ERT) with agalsidase alfa or beta. A systematic review and meta-analysis was conducted to assess the efficacy and safety of ERT for FD. Only double-blind, randomized clinical trials (RCTs) comparing agalsidase alfa or beta and placebo were included. ERT with either agalsidase alfa or beta was considered similar for the purposes of analysis. Ten RCTs were identified, which showed improvements in neuropathic pain, in heart abnormalities and in globotriaosylceramide (GL-3) levels. A meta-analysis showed increased odds for fever, rigors, development of IgG antibodies to agalsidase, and no significant association with development of hypertension or reduction in the QRS complex duration on electrocardiogram. The RCTs included in this comparison enrolled few patients, were highly heterogeneous, and were focused mainly on surrogate endpoints, limiting any conclusions as to the real effect of ERT for FD. The available evidence suggests that response to ERT is variable across patient subgroups and that agalsidase may slow progression of FD, with slight improvement of existing changes. Nevertheless, many uncertainties remain, and further studies are necessary.

Keywords: Fabry disease; Fabry disease/therapy; alpha-Galactosidase; enzyme replacement therapy.

Figure 1

Summary results under alternative values for the standard deviation for the study by Hughes et al. (2008). The blue line depicts the summary, unstandardized mean difference, whereas red and green lines denote lower and upper 95% confidence limits, respectively. Dashed line represents the null effect. Results are based on a random effects model.

Figure 2

Meta-analysis: increased odds of fever as an adverse event of enzyme replacement therapy (ERT) as compared to placebo.