Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type I Gaucher disease
Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type I Gaucher disease
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DOI：
10.1023/b:boli.0000045756.54006.17
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发表时间：
2004-01-01
影响因子：
4.2
通讯作者：
Zimran, A
中科院分区：
文献类型：
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作者：
Elstein, D;Hollak, C;Zimran, A
研究表明，麦格司他（Zelecca，N-丁基脱氧野尻霉素，OGT 918）治疗1年后可改善I型戈谢病的关键临床特征。本研究报告了长期疗效和安全性数据。完成开放标签麦格司他（100-300 mg，每日三次）治疗12个月的患者入组扩展研究继续治疗。数据显示截至第36个月。每6个月安排一次CT或MRI测量肝脏和脾脏体积。每3个月监测一次生化和血液学参数，包括壳三糖苷酶活性（戈谢病活性的敏感标志物）。每3个月收集一次安全性数据。4个中心的22名合格患者中，有18名进入扩展阶段，其中14名完成了36个月的麦格司他治疗。36个月后，所有主要疗效终点均出现统计学显著改善。肝脏和脾脏器官体积分别减少了18%和30%。在基线时血红蛋白值低于11.5 g/dl的患者中，平均血红蛋白在第12个月（NS）、第24个月（p=0.007）和第36个月（p=0.013）从基线逐渐增加0.55 g/dl、1.28 g/dl和1.30 g/dl。第36个月的平均血小板计数较基线增加22 × 10（9）/L。自既往报告以来，未发生新的周围神经病变病例。在最初12个月的研究中经常报告的腹泻和体重减轻在第二年和第三年的程度和患病率下降。接受麦格司他治疗3年的患者显示器官体积和血液学参数显着改善。总之，麦格司他的有效性随着时间的推移而增加，并且在持续治疗3年的患者中显示出可接受的耐受性。
It has been shown that treatment with miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) improves key clinical features of type I Gaucher disease after 1 year of treatment. This study reports longer-term efficacy and safety data. Patients who had completed 12 months of treatment with open-label miglustat (100-300 mg three times daily) were enrolled to continue with therapy in an extension study. Data are presented up to month 36. Liver and spleen volumes measured by CT or MRI were scheduled every 6 months. Biochemical and haematological parameters, including chitotriosidase activity (a sensitive marker of Gaucher disease activity) were monitored every 3 months. Safety data were also collected every 3 months. Eighteen of 22 eligible patients at four centres entered the extension phase and 14 of these completed 36 months of treatment with miglustat. After 36 months, there were statistically significant improvements in all major efficacy endpoints. Liver and spleen organ volumes were reduced by 18% and 30%, respectively. In patients whose haemoglobin value had been below 11.5 g/dl at baseline, mean haemoglobin increased progressively from baseline by 0.55 g/dl at month 12 (NS), 1.28 g/dl at month 24 (p=0.007), and 1.30 g/dl at month 36 (p=0.013). The mean platelet count at month 36 increased from baseline by 22x10(9)/L. No new cases of peripheral neuropathy occurred since previously reported. Diarrhoea and weight loss, which were frequently reported during the initial 12-month study, decreased in magnitude and prevalence during the second and third years. Patients treated with miglustat for 3 years show significant improvements in organ volumes and haematological parameters. In conclusion, miglustat was increasingly effective over time and showed acceptable tolerability in patients who continued with treatment for 3 years.