title: 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.
abstract: BACKGROUND
  Anderson-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.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of ERT for AFD.
  
  
  METHODS
  For 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.
  
  
  RESULTS
  77 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.
  
  
  CONCLUSIONS
  Agalsidase 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.
authors.affiliation: Institute of Science and Technology, Unesp - Univ Estadual Paulista, São José dos Campos, Brazil.|McMaster Institute of Urology, McMaster University, Hamilton, Canada.
authors.forename: Regina
authors.initials: R
authors.lastname: El Dib
authors.affiliation: Department of Pharmacy, Tanta Chest Hospital, Tanta, Egypt.
authors.forename: Huda
authors.initials: H
authors.lastname: Gomaa
authors.affiliation: IIS-Fundacion Jimenez Diaz, Universidad Autonoma Madrid, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: Neurology Service, Dr Nestor Chamoles Laboratory of Neurochemistry, Buenos Aires, Argentina.
authors.forename: Juan
authors.initials: J
authors.lastname: Politei
authors.affiliation: McMaster Institute of Urology, McMaster University, Hamilton, Canada.
authors.forename: Anil
authors.initials: A
authors.lastname: Kapoor
authors.affiliation: Department of Internal Medicine, Nephrology Service, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Fellype
authors.initials: F
authors.lastname: Barreto
mesh_terms: D015331:Cohort Studies; D056947:Enzyme Replacement Therapy / Q000379:methods*; D000795:Fabry Disease / Q000628:therapy*; D006801:Humans; D016014:Linear Models; D000519:alpha-Galactosidase / Q000627:therapeutic use*
chemical_list: D000519:alpha-Galactosidase