Enzyme replacement therapy in heterozygous females with Fabry disease: Results of a phase IIIB study
Enzyme replacement therapy in heterozygous females with Fabry disease: Results of a phase IIIB study
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DOI：
10.1023/b:boli.0000005658.14563.77
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发表时间：
2003-01-01
影响因子：
4.2
通讯作者：
Beck, M
中科院分区：
文献类型：
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作者：
Baehner, F;Kampmann, C;Beck, M
法布里病是由α-半乳糖苷酶A缺乏引起的X-连锁鞘糖脂储存障碍。受影响的患者经历使人衰弱的神经性疼痛，并且由于肾衰竭、心血管疾病或脑血管并发症而过早死亡。该疾病可能是X连锁显性遗传，因为大多数女性法布里病杂合子在临床上受到影响。我们在一项开放标签、单中心研究中评估了女性法布里病患者静脉注射半乳糖苷酶α（Replagal）的安全性、疗效和药代动力学。15例严重受累患者接受0.2 mg/kg半乳糖苷酶α，每隔一周给药一次，持续55周。半乳糖苷酶α在女性患者中安全且耐受性良好。无患者产生抗体或发生半乳糖苷酶α输注反应。女性患者中半乳糖苷酶α的药代动力学特征与男性患者中半乳糖苷酶α的药代动力学特征相当。第13、27和41周时，平均尿沉渣和血浆Gb 3水平较基线降低。在第27周（p = 0.003）和第41周（p = 0.039）观察到左心室质量较基线显著降低，在第27周观察到QRS持续时间显著缩短（p = 0.007）。此外，生活质量也有显著改善。在13- 41周的观察期内，这15例女性患者的肾功能没有恶化。我们得出结论，半乳糖苷酶α的酶替代疗法是安全和有效的女性患者杂合子法布里病。
Fabry disease is an X-linked glycosphingolipid storage disorder caused by a deficiency of alpha-galactosidase A. Affected patients experience debilitating neuropathic pain and have premature mortality due to renal failure, cardiovascular disease or cerebrovascular complications. The disease may be X-linked dominant, sincemost females heterozygous for Fabry disease are affected clinically. We evaluated the safety, efficacy and pharmacokinetics of agalsidase alfa ( Replagal) administered intravenously to female patients with Fabry disease in an open-label, single-centre study. Fifteen severely affected patients received agalsidase alfa at 0.2 mg/kg every other week for up to 55 weeks. Agalsidase alfa was safe and well-tolerated in female patients. None of the patients developed antibodies or experienced an infusion reaction to agalsidase alfa. The pharmacokinetic profile of agalsidase alfa in female patients is comparable to the pharmacokinetics of agalsidase alfa in male patients. Mean urine sediment and plasma Gb3 levels decreased from baseline at 13, 27 and 41 weeks. A significant decrease in left ventricular mass from baseline was seen at weeks 27 (p = 0.003) and 41 (p = 0.039), and a significant reduction in QRS durations was seen at week 27 (p = 0.007). Furthermore, there was a significant improvement in quality of life. Renal function did not deteriorate in these 15 female patients over the 13- to 41-week period of observation. We conclude that enzyme replacement therapy with agalsidase alfa was safe and effective in female patients heterozygous for Fabry disease.