Enzyme replacement therapy for Anderson-Fabry disease: A complementary overview of a Cochrane publication through a linear regression and a pooled analysis of proportions from cohort studies.

Regina El Dib,Huda Gomaa,Fellype Barreto,Alberto Ortiz,Anil Kapoor,Juan Politei,Leighton R James

doi:10.1371/journal.pone.0173358

Abstract

BackgroundAnderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by a deficiency of alpha-galactosidase A. Renal failure, heart and cerebrovascular involvement reduce survival. A Cochrane review provided little evidence on the use of enzyme replacement therapy (ERT). We now complement this review through a linear regression and a pooled analysis of proportions from cohort studies.ObjectivesTo evaluate the efficacy and safety of ERT for AFD.Materials and methodsFor the systematic review, a literature search was performed, from inception to March 2016, using Medline, EMBASE and LILACS. Inclusion criteria were cohort studies, patients with AFD on ERT or natural history, and at least one patient-important outcome (all-cause mortality, renal, cardiovascular or cerebrovascular events, and adverse events) reported. The pooled proportion and the confidence interval (CI) are shown for each outcome. Simple linear regressions for composite endpoints were performed.Results77 cohort studies involving 15,305 participants proved eligible. The pooled proportions were as follows: a) for renal complications, agalsidase alfa 15.3% [95% CI 0.048, 0.303; I2 = 77.2%, p = 0.0005]; agalsidase beta 6% [95% CI 0.04, 0.07; I2 = not applicable]; and untreated patients 21.4% [95% CI 0.1522, 0.2835; I2 = 89.6%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; b) for cardiovascular complications, agalsidase alfa 28% [95% CI 0.07, 0.55; I2 = 96.7%, p<0.0001]; agalsidase beta 7% [95% CI 0.05, 0.08; I2 = not applicable]; and untreated patients 26.2% [95% CI 0.149, 0.394; I2 = 98.8%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; and c) for cerebrovascular complications, agalsidase alfa 11.1% [95% CI 0.058, 0.179; I2 = 70.5%, p = 0.0024]; agalsidase beta 3.5% [95% CI 0.024, 0.046; I2 = 0%, p = 0.4209]; and untreated patients 18.3% [95% CI 0.129, 0.245; I2 = 95% p < 0.0001]. Effect differences favored agalsidase beta over agalsidase alfa or untreated patients. A linear regression showed that Fabry patients receiving agalsidase alfa are more likely to have higher rates of composite endpoints compared to those receiving agalsidase beta.ConclusionsAgalsidase beta is associated to a significantly lower incidence of renal, cardiovascular and cerebrovascular events than no ERT, and to a significantly lower incidence of cerebrovascular events than agalsidase alfa. In view of these results, the use of agalsidase beta for preventing major organ complications related to AFD can be recommended.

Highlights

Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by deficiency of alpha-galactosidase A (AGAL) which has an incidence estimated at 1 in 117,000 live births for males [1]; a recent study suggest that the incidence may be much higher, when non-classical phenotype is considered [2].The complications of AFD include major renal, cardiac and cerebrovascular events due to progressive accumulation of a globotriaosylceramide (Gb3) in numerous cell types and of deacylated Gb3 in the circulation
Enzyme replacement therapy for Anderson-Fabry disease: A complementary overview agencies played no role in the conduct of the research or preparation of the manuscript
Agalsidase beta is associated to a significantly lower incidence of renal, cardiovascular and cerebrovascular events than no enzyme replacement therapy (ERT), and to a significantly lower incidence of cerebrovascular events than agalsidase alfa. In view of these results, the use of agalsidase beta for preventing major organ complications related to AFD can be recommended

Summary

Introduction

Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by deficiency of alpha-galactosidase A (AGAL) which has an incidence estimated at 1 in 117,000 live births for males [1]; a recent study suggest that the incidence may be much higher, when non-classical phenotype is considered [2].The complications of AFD include major renal, cardiac and cerebrovascular events due to progressive accumulation of a globotriaosylceramide (Gb3) in numerous cell types and of deacylated Gb3 (globotriaosylsphingosine, lyso-Gb3) in the circulation. Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by deficiency of alpha-galactosidase A (AGAL) which has an incidence estimated at 1 in 117,000 live births for males [1]; a recent study suggest that the incidence may be much higher, when non-classical phenotype is considered [2]. Agalsidase alfa produced in human fibrosarcoma cells; while agalsidase beta is produced by a Chinese Hamster Ovary cells. Both enzymes are approved in Europe and other countries, but the Federal Drug Agency (FDA) of the United States has approved only agalsidase beta [5,6]. Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by a deficiency of alpha-galactosidase A. We complement this review through a linear regression and a pooled analysis of proportions from cohort studies

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