PURPOSE: 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.
PURPOSE: 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.
Authors: Joanna Ghali; Kathy Nicholls; Charles Denaro; David Sillence; Ian Chapman; Jack Goldblatt; Mark Thomas; Janice Fletcher Journal: JIMD Rep Date: 2011-09-15
Authors: Markus Niemann; Arndt Rolfs; Anne Giese; Hermann Mascher; Frank Breunig; Georg Ertl; Christoph Wanner; Frank Weidemann Journal: JIMD Rep Date: 2012-07-01
Authors: Saskia M Rombach; Bouwien E Smid; Gabor E Linthorst; Marcel G W Dijkgraaf; Carla E M Hollak Journal: J Inherit Metab Dis Date: 2014-02-04 Impact factor: 4.982
Authors: Markus Niemann; Tanja Hartmann; Mehdi Namdar; Frank Breunig; Meinrad Beer; Wolfram Machann; Sebastian Herrmann; Georg Ertl; Christoph Wanner; Frank Weidemann Journal: J Inherit Metab Dis Date: 2012-10-11 Impact factor: 4.982