Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease.
Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease.
复制标题
重组人酸性α-葡萄糖苷酶：对婴儿发病的庞贝氏病的主要临床益处。
作者：
P. Kishnani;D. Corzo;M. Nicolino;B. Byrne;H. Mandel;W. Hwu;N. Leslie;J. Levine;C. Spencer;M. McDonald;J. Li;J. Dumontier;M. Halberthal;Y. Chien;R. Hopkin;S. Vijayaraghavan;D. Gruskin;D. Bartholomew;A. T. van der Ploeg;J. Clancy;R. Parini;G. Morin;M. Beck;G. de la Gastine;M. Jokic;B. Thurberg;S. Richards;D. Bali;M. Davison;M. Worden;Y. Chen;J. Wraith
背景
庞贝氏症是一种进行性代谢性神经肌肉疾病，由溶酶体酸性α-葡萄糖苷酶（GAA）缺乏引起。婴儿型庞贝氏症的特征是心肌病、呼吸和骨骼肌无力以及早死。在18例快速进展性起病型庞贝氏症患者中评价了重组人（rh）GAA的安全性和有效性。
方法
患者在6个月大或更小时被诊断出患有严重的GAA缺乏症和心肌病。患者每隔一周接受20 mg/kg（n = 9）或40 mg/kg（n = 9）的rhGAA IV输注。在末例患者随机接受治疗后52周进行分析。
结果
所有患者（100%）均存活至18个月。考克斯比例风险分析表明，与未经治疗的历史对照组相比，治疗使死亡风险降低99%，使死亡或有创通气风险降低92%，使死亡或任何类型通气风险降低88%。40 mg/kg剂量在疗效方面无明显优势。18例患者中有11例发生了164例输注相关反应;所有反应的强度均为轻度或中度。
结论
重组人酸性α-葡萄糖苷酶治疗难治性庞贝氏症安全有效。11名患者发生了与治疗相关的不良事件，但没有人停止治疗。与既往重组人酸性α-葡萄糖苷酶试验中患者年龄较大相比，这些患者开始治疗的年龄较小可能有助于改善缓解。
BACKGROUND
Pompe disease is a progressive metabolic neuromuscular disorder resulting from deficiency of lysosomal acid alpha-glucosidase (GAA). Infantile-onset Pompe disease is characterized by cardiomyopathy, respiratory and skeletal muscle weakness, and early death. The safety and efficacy of recombinant human (rh) GAA were evaluated in 18 patients with rapidly progressing infantile-onset Pompe disease.
METHODS
Patients were diagnosed at 6 months of age and younger and exhibited severe GAA deficiency and cardiomyopathy. Patients received IV infusions of rhGAA at 20 mg/kg (n = 9) or 40 mg/kg (n = 9) every other week. Analyses were performed 52 weeks after the last patient was randomized to treatment.
RESULTS
All patients (100%) survived to 18 months of age. A Cox proportional hazards analysis demonstrated that treatment reduced the risk of death by 99%, reduced the risk of death or invasive ventilation by 92%, and reduced the risk of death or any type of ventilation by 88%, as compared to an untreated historical control group. There was no clear advantage of the 40-mg/kg dose with regard to efficacy. Eleven of the 18 patients experienced 164 infusion-associated reactions; all were mild or moderate in intensity.
CONCLUSIONS
Recombinant human acid alpha-glucosidase is safe and effective for treatment of infantile-onset Pompe disease. Eleven patients experienced adverse events related to treatment, but none discontinued. The young age at which these patients initiated therapy may have contributed to their improved response compared to previous trials with recombinant human acid alpha-glucosidase in which patients were older.