Miglustat in patients with Niemann-Pick disease Type C (NP-C): A multicenter observational retrospective cohort study
Miglustat in patients with Niemann-Pick disease Type C (NP-C): A multicenter observational retrospective cohort study
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DOI：
10.1016/j.ymgme.2009.07.003
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发表时间：
2009-11-01
影响因子：
3.8
通讯作者：
Patterson, M. C.
中科院分区：
文献类型：
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作者：
Pineda, M.;Wraith, J. E.;Patterson, M. C.
麦格司他已被证明可稳定C型尼曼-匹克病（NP-C）儿童、青少年和成人的疾病进展，这是一种以进行性神经功能恶化为特征的罕见遗传性疾病。我们报告了一项回顾性观察性队列研究的结果，该研究评估了麦格司他对在临床实践环境中接受治疗的患者神经系统疾病进展的影响。使用疾病残疾量表评价了在25个专家中心接受麦格司他处方的所有NP-C患者的数据。该量表分析了NP-C中神经系统疾病进展的四个关键参数（截肢、操作、语言、吞咽）。在基线（诊断时）和最多4次随访访视时计算平均单个参数评分和复合评分。总体而言，纳入了66例患者（诊断时的平均[SD]年龄为9.7 [7.6]岁，治疗开始时为12.8 [9.5]岁）。麦格司他暴露的中位（范围）为1.46（0.05-4.51）年。从诊断到治疗开始，平均年进展为+0.11评分单位/年，表明治疗前疾病进展，从治疗开始到末次临床访视，平均年进展降至-0.01评分单位/年，表明稳定。在所有年龄组中均观察到麦格司他治疗后神经系统疾病稳定，但在儿童晚期以及青少年和成人中诊断的患者中，影响程度更大。在19例具有扩展治疗前信息的患者亚组中也观察到神经系统疾病稳定。总体而言，这些数据支持既往临床试验结果，表明麦格司他对NP-C患者神经系统疾病进展具有临床相关获益作用。(C)2009 Elsevier Inc. All rights reserved.
Miglustat has been shown to stabilize disease progression in children, juveniles and adults with Niemann-Pick disease type C (NP-C), a rare genetic disorder characterized by progressive neurological deterioration. We report findings from a retrospective observational cohort study assessing the effects of miglustat on neurological disease progression in patients treated in the clinical practice setting. Data from all NP-C patients prescribed miglustat at 25 expert centers were evaluated using a disease disability scale. The scale analyzed four key parameters of neurological disease progression in NP-C (ambulation, manipulation, language, swallowing). Mean individual parameter scores and a composite score were calculated at baseline (time of diagnosis) and up to 4 follow-up visits. Overall, 66 patients were included (mean [SD] age at diagnosis, 9.7 [7.6] years, and at treatment start, 12.8 [9.5] years). The median (range) miglustat exposure was 1.46 (0.05-4.51) years. Mean annual progression was +0.11 score units/year from diagnosis to treatment start, indicating disease progression prior to therapy, and decreasing to -0.01 score units/year from treatment start to last clinic visit, indicating stabilization. Stabilization of neurological disease on miglustat was observed in all age groups, but the magnitude of the effect was greater in patients diagnosed in late childhood and in juveniles and adults. Stabilization of neurological disease was also observed in a subset of 19 patients with extended pre-treatment information. Overall, these data support previous clinical trial findings indicating clinically relevant beneficial effects of miglustat on neurological disease progression in patients with NP-C. (C) 2009 Elsevier Inc. All rights reserved.