Fabry disease: overall effects of agalsidase alfa treatment.
BACKGROUND
Fabry disease is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. Progressive accumulation of the substrate globotriaosylceramide in cells throughout the body leads to major organ failure and premature death. The Fabry Outcome Survey (FOS) is a European outcomes database which was established to collect data on the natural history of this little-known disease and to monitor the long-term efficacy and safety of enzyme replacement therapy (ERT) with agalsidase alfa. This paper presents the first analysis of the FOS database on the effects of ERT on renal function, heart size, pain and quality of life.


METHODS
The effects of 1 and 2 years of ERT with agalsidase alfa on renal function (assessed by estimated glomerular filtration rate), heart size (assessed by echocardiography), pain (assessed by the Brief Pain Inventory) and quality of life (assessed by the European Quality of Life Questionnaire EQ-5D) were analyzed in a cohort of 545 patients, 314 of whom were receiving treatment (188 for at least 12 months and 92 for at least 24 months; mean duration of treatment, 17 months; maximum duration, 56 months).


RESULTS
Treatment with agalsidase alfa stabilized renal function in patients with a mild or moderate deterioration in renal function at baseline, reduced left ventricular size in patients who had an enlarged heart at baseline, and improved pain scores and quality of life. These improvements were similar in hemizygous men and heterozygous women with Fabry disease.


CONCLUSIONS
Enzyme replacement therapy with agalsidase alfa leads to significant clinical benefits in patients with Fabry disease, and treatment is likely to alter the natural history of this disorder.
Beck
M
M
Department of Paediatrics, University of Mainz, Mainz, Germany. beck@kinder.klinik.uni-mainz.de
Ricci
R
R
Widmer
U
U
Dehout
F
F
de Lorenzo
A García
AG
Kampmann
C
C
Linhart
A
A
Sunder-Plassmann
G
G
Houge
G
G
Ramaswami
U
U
Gal
A
A
Mehta
A
A
D000328:Adult; D016208:Databases, Factual; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D007527:Isoenzymes / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D011788:Quality of Life; D011994:Recombinant Proteins; D016896:Treatment Outcome; D000519:alpha-Galactosidase / Q000009:adverse effects / Q000627:therapeutic use*
D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase