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Schiffmann R, Kopp JB, Austin III HA, et al. Enzyme Replacement Therapy in Fabry Disease: A Randomized Controlled Trial. JAMA. 2001;285(21):2743–2749. doi:https://doi.org/10.1001/jama.285.21.2743
Author Affiliations: Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke (Drs Schiffmann, Moore, Weibel, and Brady), and Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases (Drs Kopp, Austin, and Balow), National Institutes of Health, Bethesda, Md; Division of Nephropathology, Armed Forces Institute of Pathology, Washington, DC (Dr Sabnis).
Context Fabry disease is a metabolic disorder without a specific treatment,
caused by a deficiency of the lysosomal enzyme α-galactosidase A (α-gal
A). Most patients experience debilitating neuropathic pain and premature mortality
because of renal failure, cardiovascular disease, or cerebrovascular disease.
Objective To evaluate the safety and efficacy of intravenous α-gal A for
Design and Setting Double-blind placebo-controlled trial conducted from December 1998 to
August 1999 at the Clinical Research Center of the National Institutes of
Patients Twenty-six hemizygous male patients, aged 18 years or older, with Fabry
disease that was confirmed by α-gal A assay.
Intervention A dosage of 0.2 mg/kg of α-gal A, administered intravenously every
other week (12 doses total).
Main Outcome Measure Effect of therapy on neuropathic pain while without neuropathic pain
medications measured by question 3 of the Brief Pain Inventory (BPI).
Results Mean (SE) BPI neuropathic pain severity score declined from 6.2 (0.46)
to 4.3 (0.73) in patients treated with α-gal A vs no significant change
in the placebo group (P = .02). Pain-related quality
of life declined from 3.2 (0.55) to 2.1 (0.56) for patients receiving α-gal
A vs 4.8 (0.59) to 4.2 (0.74) for placebo (P = .05).
In the kidney, glomeruli with mesangial widening decreased by a mean of 12.5%
for patients receiving α-gal vs a 16.5% increase for placebo (P = .01). Mean inulin clearance decreased by 6.2 mL/min
for patients receiving α-gal A vs 19.5 mL/min for placebo (P = .19). Mean creatinine clearance increased by 2.1 mL/min (0.4 mL/s)
for patients receiving α-gal A vs a decrease of 16.1 mL/min (0.3 mL/s)
for placebo (P = .02). In patients treated with α-gal
A, there was an approximately 50% reduction in plasma glycosphingolipid levels,
a significant improvement in cardiac conduction, and a significant increase
in body weight.
Conclusion Intravenous infusions of α-gal A are safe and have widespread
therapeutic efficacy in Fabry disease.
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