Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting

Raphael Schiffmann, Markus Ries, Margaret Timmons, John T Flaherty, Roscoe O Brady
Nephrology, Dialysis, Transplantation 2006, 21 (2): 345-54

BACKGROUND: Fabry disease is an X-linked disorder of glycosphingolipid catabolism that is the result of an intracellular deficiency in the lysosomal enzyme alpha-galactosidase A (alpha-Gal A). This enzymatic defect results in the accumulation of globotriaosylceramide (Gb(3)) within cells and causes progressive neurological, cardiovascular and renal dysfunction. Our objective is to describe the safety and renal effects of long-term enzyme replacement therapy.

METHODS: This was a single centre, prospective open-label treatment trial in 25 adult male Fabry patients who had completed a 6-month randomized placebo-controlled study and subsequently enrolled in an open-label extension study. Patients were treated every other week with agalsidase alfa (0.2 mg/kg) infused intravenously over 40 min. The main outcome measures were safety, antibody response and renal glomerular filtration rate (GFR).

RESULTS: During the 4-4.5 years of enzyme replacement therapy, all eligible subjects were able to transition to home therapy. Eight patients developed persistent IgG antibodies to agalsidase alfa, but IgE antibodies were not detected in any patient. The development of IgG antibodies appeared not to affect any clinical end points. Estimated GFR remained stable in subgroups of patients with Stage I (GFR >90 ml/min) or Stage II (GFR 60-89 ml/min) chronic kidney disease at baseline. In contrast, in the subgroup of patients with Stage III chronic kidney disease (GFR 30-59 ml/min), the slope of the decline in GFR was reduced compared with comparable historical controls, suggesting that enzyme replacement therapy was slowing the decline of renal function in this susceptible population.

CONCLUSIONS: Long-term enzyme replacement therapy with agalsidase alfa is safe and may slow the progressive decline in renal function that was commonly observed in adult males with Fabry disease.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"