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.

Long‐term effectiveness of enzyme replacement therapy in Fabry disease: results from the NCS‐LSD cohort study

“…Finally, this study was severely weakened by the lack of consistency in assessing and recording key outcomes which led to substantial amounts of missing data. The issues related to recording clinical endpoints have been recognised as posing a substantial problem in comparing and drawing robust conclusions when looking at treatment efficacy in diseases such as Fabry disease (Alegra et al 2012).…”

“…Since this time, evidence of efficacy has been largely derived from small, poor quality, randomised controlled trial (RCTs) which provide no robust evidence for use of either therapy to treat Fabry disease. Over 20 publications from six RCTs have been identified and reviewed by three separate systematic reviews of ERT effectiveness in Fabry disease (Connock et al 2006;Alegra et al 2012;E l Dib et al 2013). Results suggest some beneficial effect of ERT on measures of pain and cardiovascular function and stabilisation of renal function, while there is no convincing evidence for an effect on neurological events (Connock et al 2006).…”

The neurological manifestations of Fabry disease. A review

“…Она позволяет уменьшить нейро-патическую боль [91][92][93][94][95][96][97], улучшить функционирование различных типов нервных волокон иинтрадермальных ре-цепторов вибрации [98], также отмечается улучшение функции потооделения, переносимость жары, темпера-турная чувствительность [99,100]. Наблюдается положи-тельная динамика при лечении синдрома беспокойных ног [101].…”

Fabry Nephropathy: An Evidence-Based Narrative Review

“…Accordingly, agalsidase alfa and agalsidase beta have different optimal dosing regimens [6,7]. The introduction of ERT provided the first opportunity to address the underlying enzyme deficiency, allowing the removal of part of the Gb3 deposits, improvement of Fabryrelated symptoms and (potential) protection of severely affected organs [11][12][13]. However, a considerable number of FD patients develop disease manifestations despite treatment [14].…”