Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center-University Hospital Sophia Children's Hospital, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands.
Mol Genet Metab. 2012 Nov;107(3):456-61. doi: 10.1016/j.ymgme.2012.09.015. Epub 2012 Sep 17.
Late-onset Pompe disease is a progressive, debilitating, and often fatal neuromuscular disorder resulting from the deficiency of a lysosomal enzyme, acid α-glucosidase. This extension study was conducted to determine the durability of the efficacy and safety of alglucosidase alfa observed over a period of 78 weeks in the Late-Onset Treatment Study (LOTS).
Patients who completed the LOTS study were eligible for this open-label extension study and received alglucosidase alfa 20mg/kg biweekly for an additional 26 weeks. The primary efficacy assessments were the distance walked during a 6-minute walk test and the percentage of predicted forced vital capacity in the upright position. Data are reported as change from patient's original LOTS baseline for each measure.
The benefit of alglucosidase alfa treatment observed in LOTS at Week 78 was, in general, maintained at Week 104. The mean increase in distance walked measured 28.2 ± 66.5m from LOTS baseline to Week 78 and 21.3 ± 78.0m from LOTS baseline to Week 104. The mean change from baseline in percentage of predicted forced vital capacity was 1.3% ± 5.7% from LOTS baseline to Week 78 and 0.8% ± 6.7% from LOTS baseline to Week 104. Treatment-related adverse events were mainly infusion-associated reactions observed in 35% of patients. No deaths or anaphylactic reactions were observed during the extension study.
The LOTS Extension study showed that patients treated with alglucosidase alfa for up to 104 weeks maintained the improved walking distance and stabilization in pulmonary function observed in the first 78 weeks of alglucosidase alfa therapy.
迟发性庞贝病是一种进行性、使人虚弱且常致命的神经肌肉疾病,由溶酶体酶酸性α-葡萄糖苷酶的缺乏引起。本扩展研究旨在确定阿糖苷酶α在长达 78 周的迟发型治疗研究(LOTS)中观察到的疗效和安全性的持久性。
完成 LOTS 研究的患者有资格参加本开放标签扩展研究,并接受每周两次 20mg/kg 的阿糖苷酶α治疗,再持续 26 周。主要疗效评估是 6 分钟步行试验中行走的距离和直立位预测用力肺活量的百分比。数据报告为每个测量指标相对于患者原始 LOTS 基线的变化。
LOTS 研究中第 78 周观察到的阿糖苷酶α治疗的益处通常在第 104 周保持。从 LOTS 基线到第 78 周,步行距离的平均增加量为 28.2±66.5m,从 LOTS 基线到第 104 周为 21.3±78.0m。从 LOTS 基线到第 78 周,预测用力肺活量百分比的平均变化为 1.3%±5.7%,从 LOTS 基线到第 104 周为 0.8%±6.7%。与治疗相关的不良事件主要是 35%的患者出现的输注相关反应。在扩展研究期间未观察到死亡或过敏反应。
LOTS 扩展研究表明,接受阿糖苷酶α治疗长达 104 周的患者保持了第 1-78 周阿糖苷酶α治疗中观察到的改善的步行距离和肺功能稳定。