Abstract | CONTEXT: OBJECTIVES: METHODS: We conducted a 6-month open-label study at 3 tertiary care centers with 24 children (19 boys and 5 girls) with a mean age of 11.8 (range: 6.5-18) years, to examine safety parameters, including infusion reactions and antiagalsidase alfa antibodies. RESULTS:
Agalsidase alfa was well tolerated, and all of the patients completed the study. Six boys and 1 girl had mild-to-moderate infusion reactions. One boy developed transient immunoglobulin G antibodies against agalsidase alfa. The boys showed a significant reduction in plasma globotriaosylceramide on treatment. Mean estimated glomerular filtration rate, cardiac structure, and function were normal and did not change over 26 weeks. Heart rate variability, as determined by 2-hour ambulatory monitoring, was decreased in the boys compared with the girls at baseline. All indices of heart rate variability improved significantly in the boys. Three patients with anhidrosis, as determined by quantitative sudomotor axon reflex testing, developed sweating. Six of 11 patients could reduce or cease their use of antineuropathic analgesics. CONCLUSIONS:
Enzyme replacement with agalsidase alfa was safe in this study. The exploratory efficacy analysis documented increased clearance of globotriaosylceramide and improvement of autonomic function. Prospective long-term studies are needed to assess whether enzyme replacement initiated early in patients with Fabry disease is able to prevent major organ failure in adulthood.
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Authors | Markus Ries, Joe T R Clarke, Catharina Whybra, Margaret Timmons, Chevalia Robinson, Bradley L Schlaggar, Gregory Pastores, Y Howard Lien, Christoph Kampmann, Roscoe O Brady, Michael Beck, Raphael Schiffmann |
Journal | Pediatrics
(Pediatrics)
Vol. 118
Issue 3
Pg. 924-32
(Sep 2006)
ISSN: 1098-4275 [Electronic] United States |
PMID | 16950982
(Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Intramural)
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Chemical References |
- Isoenzymes
- Recombinant Proteins
- agalsidase alfa
- alpha-Galactosidase
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Topics |
- Adolescent
- Antibody Formation
- Autonomic Nervous System
(drug effects)
- Child
- Fabry Disease
(drug therapy)
- Female
- Heart Rate
(drug effects)
- Humans
- Isoenzymes
(adverse effects, therapeutic use)
- Male
- Recombinant Proteins
- Treatment Outcome
- alpha-Galactosidase
(adverse effects, therapeutic use)
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