Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease
Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease
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DOI：
10.1097/gim.0b013e31819d0996
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发表时间：
2009-03-01
影响因子：
8.8
通讯作者：
Kishnani, Priya S.
中科院分区：
文献类型：
--
作者：
Nicolino, Marc;Byrne, Barrv;Kishnani, Priya S.
目的：评价α-葡萄糖苷酶治疗婴幼儿晚期Pompe病的安全性和有效性。方法：对21例超声心动图显示低酸性α-葡萄糖苷酶活性和左心室重量指数异常的3~43个月(中位13个月)的婴儿进行开放标记的多中心研究。患者每2周静脉注射α-葡萄糖苷酶，持续时间长达168周(中位数120周)。生存结果与未经TIN治疗的参考队列进行比较。结果：研究结束时，71%(15/21)的患者存活，44%(7/16)的无创呼吸机患者仍然存活。与未经治疗的参考队列相比，α-葡萄糖苷酶降低了79%的死亡风险(P<；0.001)和58%的有创机械通气风险(P=0.02)。在所有评估超过12周的患者中，左心室质量指数改善或保持正常；62%(13/21)实现了新的运动里程碑。5例患者在研究结束时独立行走，86%(18/21)患者获得了功能独立技能。总体而言，52%(11/21)的患者经历了输液相关反应；95%(19/20)的患者产生了重组人溶酶体酸a-葡萄糖苷酶的抗体；没有患者因安全考虑而退出研究。结论：在这群患有晚期疾病的婴儿中，两周一次的α-糖苷酶输注延长了存活期和侵入性呼吸机逃逸存活率。治疗还改善了心肌病、运动技能和功能独立性的指数。Genet Med 2009：11(3)：210-219。
Purpose: A clinical trial was conducted to evaluate the safety and efficacy of alglucosidase alfa in infants and children with advanced Pompe disease. Methods: Open-label, multicenter study of IV alglucosidase alfa treatment in 21 infants 3-43 months old (median 13 months) with minimal acid a-glucosidase activity and abnormal left ventricular mass index by echo-cardiography. Patients received IV alglucosidase alfa every 2 weeks for up to 168 weeks (median 120 weeks). Survival results were compared with tin untreated reference cohort. Results: At study end, 71% (15/21) of patients were alive and 44% (7/16) of invasive-ventilator free patients remained so. Compared with the untreated reference cohort, alglucosidase alfa reduced the risk of death by 79% (P < 0.001) and the risk of invasive ventilation by 58% (P = 0.02). Left ventricular mass index improved or remained normal in all patients evaluated beyond 12 weeks; 62% (13/21) achieved new motor milestones. Five patients were walking independently at the end of the study and 86% (18/21) gained functional independence skills. Overall, 52% (11/21) of patients experienced infusion-associated reactions; 95% (19/20) developed IgG antibodies to recombinant human lysosomal acid a-glucosidase; no patients withdrew from the study because of safety concerns. Conclusions: In this population of infants with advanced disease, biweekly infusions with alglucosidase alfa prolonged survival and invasive ventilation-flee survival. Treatment also improved indices of cardiomyopathy, motor skills, and functional independence. Genet Med 2009:11(3):210-219.