Enzyme replacement therapy for Anderson-Fabry disease

Abstract

Background: Anderson-Fabry disease is an X-linked defect of glycosphingolipid metabolism. Progressive renal insufficiency is a major source of morbidity, additional complications result from cardio- and cerebro-vascular involvement. Survival is reduced among affected males and symptomatic female carriers.

Objectives: To evaluate the effectiveness and safety of enzyme replacement therapy compared to other interventions, placebo or no interventions, for treating Anderson-Fabry disease.

Search strategy: We searched 'Clinical Trials' on The Cochrane Library, MEDLINE, EMBASE, LILACS and the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register (date of the most recent search: 07 April 2010).

Selection criteria: Randomized controlled trials of agalsidase alfa or beta in participants diagnosed with Anderson-Fabry disease.

Data collection and analysis: Two authors selected relevant trials, assessed methodological quality and extracted data.

Main results: Five studies comparing either agalsidase alfa or beta in 187 participants fulfilled the selection criteria.Both trials comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma and tissue; aggregate results were non-significant. One study reported pain scores, there was a statistically significant improvement for participants receiving treatment at up to three months, mean difference -2.10 (95% confidence interval (CI) -3.79 to -0.41); at up to five months, mean difference -1.90 (95% CI -3.65 to -0.15); and at up to six months, mean difference -2.00 (95% CI -3.66 to -0.34). There was a significant difference in pain-related quality of life at over five months and up to six months, mean difference -2.10 (95% CI -3.92 to -0.28) but not at other time-points. Neither study reported deaths.One of the three trials comparing agalsidase beta to placebo reported on globotriaosylceramide concentration in plasma and tissue and showed significant improvement: kidney, mean difference -1.70 (95% CI -2.09 to -1.31); heart, mean difference -0.90 (95% CI -1.18 to -0.62); and composite results (renal, cardiac, and cerebrovascular complications and death), mean difference -4.80 (95% CI -5.45 to -4.15). There was no significant difference between groups for death; no studies reported on pain.

Authors' conclusions: Five small, poor quality randomised controlled trials provide no robust evidence for use of either agalsidase alfa and beta to treat Anderson-Fabry disease.