A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease.
OBJECTIVE
Although Fabry disease is X linked and considered to affect primarily male hemizygotes, female heterozygotes may experience all the signs and symptoms of this metabolic disorder. This prospective, single-center, open-label, clinical trial was performed to evaluate the long-term response of female patients with Fabry disease to enzyme replacement therapy.


METHODS
Symptomatic women (average age = 47 years) enrolled in this 4-year study were treated with agalsidase alfa (Replagal, Shire HGT, Inc.) at a dose of 0.2 mg/kg, every other week for 4 years (N = 36). Clinical and biochemical assessments were conducted at 12-month intervals.


RESULTS
The Mainz Severity Score Index, a measure of total disease burden, was significantly reduced after 12 months (P < 0.01) of treatment and continuously improved over 4 years. Brief Pain Inventory "pain at its worst" score was reduced from 4.6 +/- 2.9 at baseline to 3.3 +/- 2.9 after 12 months (P = 0.001) and remained reduced through 4 years. Mean left-ventricular mass decreased from 89.4 +/- 29.3(2.7) g/m at baseline to 66.5 +/- 29.3(2.7) g/m after 12 months (P < 0.001) and remained reduced through 4 years. Average kidney function (estimated glomerular filtration rate and proteinuria) remained constant during the study. No safety issues were identified.


CONCLUSIONS
Long-term agalsidase alfa is effective and was well tolerated in women with Fabry disease.
Center for Lysosomal Storage Diseases, Children's Hospital of Johannes Gutenberg University, Mainz, Germany.
Catharina
C
Whybra
Elke
E
Miebach
Eugen
E
Mengel
Andreas
A
Gal
Karin
K
Baron
Michael
M
Beck
Christoph
C
Kampmann
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D004334:Drug Administration Schedule; D000795:Fabry Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000627:therapeutic use; D007962:Leukocytes / Q000201:enzymology; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D011994:Recombinant Proteins; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*
D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase