Enzyme replacement therapy for Anderson-Fabry disease

Area of Science:

• Genetics and Metabolism
• Pharmacology
• Clinical Trials

Background:

• Anderson-Fabry disease is an X-linked genetic disorder impacting glycosphingolipid metabolism.
• It leads to progressive renal insufficiency, cardiovascular, and cerebrovascular complications.
• Reduced survival rates are observed in affected males and symptomatic female carriers.

Purpose of the Study:

• To evaluate the efficacy and safety of enzyme replacement therapy (ERT) for Anderson-Fabry disease.
• Comparisons include other interventions, placebo, or no treatment.
• This review updates previous Cochrane analyses from 2010 and 2013.

Main Methods:

• Searched multiple databases including the Cystic Fibrosis and Genetic Disorders Group's register, Clinical Trials, MEDLINE, Embase, and LILACS.
• Included randomized controlled trials (RCTs) of agalsidase alfa or beta for Anderson-Fabry disease.
• Two authors independently selected trials, assessed quality, and extracted data.

Main Results:

• Nine RCTs involving 351 participants were analyzed.
• Agalsidase alfa showed non-significant improvements in globotriaosylceramide levels but improved pain and quality of life.
• Agalsidase beta demonstrated significant improvements in globotriaosylceramide levels and composite outcomes, but not pain or mortality.

Conclusions:

• ERT significantly improves microvascular deposits and pain-related quality of life in Anderson-Fabry disease.
• Evidence is insufficient to determine superiority of agalsidase alfa vs. beta or optimal dosing.
• Long-term impact on morbidity and mortality remains undetermined, necessitating further research.