Chinese hamster ovary cell-derived recombinant human acid α-glucosidase in infantile-onset Pompe disease
Chinese hamster ovary cell-derived recombinant human acid α-glucosidase in infantile-onset Pompe disease
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DOI：
10.1016/j.jpeds.2006.02.035
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发表时间：
2006-07-01
影响因子：
5.1
通讯作者：
Chen, Y. T.
中科院分区：
文献类型：
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作者：
Kishnani, Priya Sunil;Nicolino, Marc;Chen, Y. T.
目的：进行一项开放标签、多国家、多中心研究，检查重组人酸性α-葡萄糖苷酶（rhGAA）治疗婴儿型庞贝氏症的安全性和有效性。研究设计：我们招募了8例患有庞贝氏症的婴儿患者，GAA活性<正常值的1%，心肌病和肌张力减退。在52周的初始阶段，每周以10 mg/kg静脉输注rhGAA;扩展阶段继续以每周10至20 mg/kg或每2周20 mg/kg的rhGAA治疗存活者，持续153周。安全性测量包括不良事件、实验室检查和抗rhGAA抗体滴度。结果：治疗52周后，8例患者中6例存活，5例脱离有创呼吸机支持，5例无创呼吸机支持，1例无创呼吸机支持。临床改善包括心肌病改善以及生长和认知改善。5例患者获得新的运动里程碑; 3例患者独立行走。4例患者在初始研究阶段后死亡;所有患者死亡或停药时的中位年龄为21.7个月，显著晚于未接受治疗患者的预期年龄。治疗是安全的，耐受性良好：没有死亡是drug-related.Conclusion：rhGAA改善无呼吸机生存，心肌病，生长，运动功能与预期的结果相比，患者没有接受治疗的患者与起病庞贝氏症。
Objective: To conduct an open-label, multinational, multicenter study examining the safety and efficacy of recombinant human acid alpha-glucosidase (rhGAA) in treatment of infantile-onset Pompe disease.Study design: We enrolled 8 infant patients who had Pompe disease with GAA activity < 1% of normal, cardiomyopathy, and hypotonia. In the 52-week initial phase, rhGAA was infused intravenously at 10 mg/kg weekly; an extension phase continued survivors' treatment with 10 to 20 mg/kg of rhGAA weekly or 20 mg/kg every 2 weeks for as long its 153 weeks. Safety measurements included adverse events, laboratory tests, and anti-rhGAA antibody titers. Efficacy evaluations included survival, ventilator use echo- cardiograms growth and motor and cognitive function.Result: After 52 weeks of treatment, 6 of 8 patients were alive, mid 5 patients were free of invasive ventilator support. Clinical improvements included ameliorated cardiomyopathy and improved growth and cognition. Five patients acquired new motor milestones; 3 patients walked independently. Four patients died after the initial study phase; the median age at death or treatment withdrawal for all patients was 21.7 months, significantly later than expected for patients who were not treated. Treatment was safe and well tolerated: no death was drug-related.Conclusion: rhGAA improved ventilator-free survival, cardiomyopathy, growth, and motor function in patients with infantile-onset Pompe disease compared with outcomes expected for patients without treatment.