ArticlesEnzyme replacement therapy with agalsidase alfa in patients with Fabry's disease: an analysis of registry data
Introduction
Fabry's disease is a rare progressive multisystem disorder resulting from deficiency of the lysosomal enzyme α-galactosidase A. Renal failure, cardiomyopathy, and cerebrovascular disease are the main causes of morbidity and premature death.1 During the past 8 years, results of randomised controlled trials and clinical studies of the two preparations of enzyme replacement therapy, agalsidase alfa (Shire Human Genetic Therapies [HGT]) and agalsidase beta (Genzyme Corporation), have shown the safety and efficacy of treatment in small groups of adults and children with Fabry's disease.2, 3, 4, 5, 6, 7 Two observational databases, the Fabry Outcome Survey (FOS) and the Fabry Registry, follow the treatment of patients receiving agalsidase alfa and agalsidase beta, respectively. Data from these registries extend our knowledge of the natural history of the disease and its response to enzyme replacement therapy.1, 8, 9, 10, 11 We report FOS data for the effects of 5 years of treatment with agalsidase alfa on cardiac mass and function, renal function, pain, and quality of life.
Section snippets
Patients
FOS was approved by ethics institution review boards of participating centres. Patients gave written informed consent and were either receiving or not receiving enzyme replacement therapy with agalsidase alfa. No patient received agalsidase beta during the study. Every patient's medical history was documented by a physician or nurse specialist, including year of diagnosis, signs and symptoms, treatment, demographic details, and family history. Results of routine clinical assessments or
Results
At the time of analysis (database locked October, 2007), FOS contained data for 1428 patients from 19 countries, of whom 692 (607 adults) were receiving agalsidase alfa. 5-year longitudinal data were not available for most patients because therapy was continuing. Baseline and 5-year follow-up data were available for 181 adults (mean age 39·2 [12·3] years; 126 men; 176 (97·2%) Caucasian). Mutation data were available for 152 patients (102 men): 75 missense mutations (52 men), 35 non-sense
Discussion
We report long-term data for the effects of enzyme replacement therapy with agalsidase alfa on cardiac mass and function, renal function, pain, and quality of life in a large group of patients enrolled in FOS. Our results show sustained benefits of agalsidase alfa during 5 years of treatment. Patients with LVH at baseline had a clinically significant reduction in LVH during the 5 years and an improvement in myocardial contractility during the first 3 years of treatment. In patients with normal
References (31)
- et al.
Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings
Am J Cardiol
(1986) - et al.
Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology
J Am Soc Echocardiogr
(2005) - et al.
Validation of the Brief Pain Inventory for chronic nonmalignant pain
J Pain
(2004) - et al.
CNS manifestations of Fabry's disease
Lancet Neurol
(2006) - et al.
Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey
Eur J Clin Invest
(2004) - et al.
Enzyme replacement therapy in Fabry disease: a randomized controlled trial
JAMA
(2001) - et al.
Safety and efficacy of recombinant human alpha-galactosidase A-replacement therapy in Fabry's disease
N Engl J Med
(2001) - et al.
Effects of enzyme replacement therapy on the cardiomyopathy of Anderson–Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa
Heart
(2008) - et al.
Agalsidase-beta therapy for advanced Fabry disease: a randomized trial
Ann Intern Med
(2007) - et al.
Enzyme replacement therapy with agalsidase alfa in children with Fabry disease
Acta Paediatr
(2007)
Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease
J Pediatr
Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry
J Inherit Metab Dis
Enzyme replacement therapy and renal function in 201 patients with Fabry disease
Clin Nephrol
Effects of enzyme replacement therapy on pain and health related quality of life in patients with Fabry disease: data from FOS (Fabry Outcome Survey)
J Med Genet
Agalsidase alfa slows the decline in renal function in patients with Fabry disease
Am J Nephrol
Cited by (244)
Long-term follow-up of renal function in patients treated with migalastat for Fabry disease
2021, Molecular Genetics and Metabolism ReportsIn Vitro and In Vivo Amenability to Migalastat in Fabry Disease
2020, Molecular Therapy Methods and Clinical DevelopmentFabry Disease: More than a Phenocopy of Hypertrophic Cardiomyopathy
2023, Journal of Clinical MedicineMorphological Hallmarks of Classical Fabry Disease: An Ultrastructural Study in a Large Spanish Family
2023, Journal of Clinical Medicine
- ‡
Listed at end of paper