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

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

Journal of Medical Ethics

Texto completo: acesso restrito. p. 233-239Background/Aims Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disorder treated with bone marrow transplantation or enzyme replacement therapy with laronidase, a high-cost orphan drug. Laronidase was approved by the US Food and Drug Administration and the European Medicines Agency in 2003 and by the Brazilian National Health Surveillance Agency in 2005. Many Brazilian MPS I patients have been receiving laronidase despite the absence of a governmental policy regulating access to the drug. Epidemiological and treatment data concerning MPS I are scarce. This study aims to present a demographic profile of Brazilian patients with MPS I, describe the routes of access to laronidase in Brazil, and discuss associated ethical issues relating to public funding of orphan drugs. Methods In this cross-sectional observational study, data were collected nationwide between January and September 2008 from physicians, public institutions and non-governmental organisations involved with diagnosis and treatment of MPS I, using two data collection instruments specifically designed for this purpose. Results The minimum prevalence of MPS I in Brazil was estimated at 1/2 700 000. Most patients (69.8%) were younger than 15 years; 60 (88.2%) received laronidase. The most common route of access to the drug was through lawsuits (86.6%). Conclusions In Brazil, MPS I is predominantly a paediatric illness. Even though the cost of laronidase treatment is not officially covered by the Brazilian government, most MPS I patients receive the drug, usually through litigation. This gives rise to major ethical conflicts concerning drug access in a low-resource context. The Brazilian health policy framework lacks evidence-based clinical protocols for the distribution of orphan drugs