A Randomized Study of Alglucosidase Alfa in Late-Onset Pompe's Disease.
A Randomized Study of Alglucosidase Alfa in Late-Onset Pompe's Disease.
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DOI：
10.1056/nejmoa0909859
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发表时间：
2010-04-15
影响因子：
158.5
通讯作者：
Zivkovic, Sasa A.
中科院分区：
文献类型：
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作者：
van der Ploeg, Ans T.;Clemens, Paula R.;Zivkovic, Sasa A.
背景：Pompe病是一种由酸性α葡萄糖苷酶(GAA)缺乏引起的代谢性肌病，GAA是一种降解溶酶体糖原的酶。迟发性庞培病的特征是进行性肌肉无力和呼吸功能丧失，导致过早死亡。我们进行了一项随机、安慰剂对照的阿尔法葡萄糖苷酶试验，一种重组人GAA，用于治疗晚发型Pompe‘s病。方法：在美国和欧洲的8个中心，90名年龄在8岁或以上、不能进行有创呼吸机治疗的患者被随机分配到两周一次的静脉注射阿尔法葡萄糖苷酶(每公斤体重20毫克)或安慰剂治疗78周。两个主要终点是6分钟步行试验的步行距离和预计用力肺活量的百分比。结果：78周时，主要终点的估计平均值变化有利于α-葡萄糖苷酶(6分钟步行试验增加28.1+/-13.1m，用力肺活量绝对增加3.4/-1.2个百分点；P=0.03和P=0.006)。两组患者的不良事件、严重不良事件和输液相关反应的比例相似；仅在接受活性研究药物的患者中发生的事件包括过敏反应和输液相关反应，包括荨麻疹、潮红、多汗、胸部不适、呕吐和血压升高(每种反应都发生在5%到8%的患者中)。结论：在本研究人群中，在18个月的时间里，使用阿尔法葡萄糖苷酶治疗与改善步行距离和肺功能稳定有关。(ClinicalTrials.gov编号，NCT00158600)N Engl J Med 2010；362：1396-406。
Background: Pompe's disease is a metabolic myopathy caused by a deficiency of acid alpha glucosidase (GAA), an enzyme that degrades lysosomal glycogen. Late-onset Pompe's disease is characterized by progressive muscle weakness and loss of respiratory function, leading to early death. We conducted a randomized, placebo-controlled trial of alglucosidase alfa, a recombinant human GAA, for the treatment of late-onset Pompe's disease.Methods: Ninety patients who were 8 years of age or older, ambulatory, and free of invasive ventilation were randomly assigned to receive biweekly intravenous alglucosidase alfa (20 mg per kilogram of body weight) or placebo for 78 weeks at eight centers in the United States and Europe. The two primary end points were distance walked during a 6-minute walk test and percentage of predicted forced vital capacity (FVC).Results: At 78 weeks, the estimated mean changes from baseline in the primary end points favored alglucosidase alfa (an increase of 28.1+/-13.1 m on the 6-minute walk test and an absolute increase of 3.4+/-1.2 percentage points in FVC; P=0.03 and P=0.006, respectively). Similar proportions of patients in the two groups had adverse events, serious adverse events, and infusion-associated reactions; events that occurred only in patients who received the active study drug included anaphylactic reactions and infusion-associated reactions of urticaria, flushing, hyperhidrosis, chest discomfort, vomiting, and increased blood pressure (each of which occurred in 5 to 8% of the patients).Conclusions: In this study population, treatment with alglucosidase alfa was associated with improved walking distance and stabilization of pulmonary function over an 18-month period. (ClinicalTrials.gov number, NCT00158600.)N Engl J Med 2010;362:1396-406.