Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul, Korea.
Dev Med Child Neurol. 2011 Mar;53(3):239-44. doi: 10.1111/j.1469-8749.2010.03830.x. Epub 2010 Nov 18.
The aim of this study was to evaluate the efficacy and safety of a newly manufactured botulinum toxin, Neuronox, compared with BOTOX for the treatment of the spastic equinus gait in children with cerebral palsy.
A total of 127 children with cerebral palsy, aged 2 to 10 years, who presented at three university hospitals with spastic equinus gait were assessed for eligibility to participate in this double-blinded, randomized, controlled trial. Of the 119 eligible participants (mean age 4.33 y; SD 2.07; 76 males and 43 females; 79 with diplegia and 40 with hemiplegia), 57 were classified as Gross Motor Function Classification System level I, 29 as level II, and 33 as level III. Participants were randomly assigned to receive an injection of Neuronox (n=60) or BOTOX (n=59) to the calf muscles at a dose of 4U/kg for those with hemiplegia and 6U/kg for those with diplegia. Assessments were performed at baseline (V1) and at 4 (V2), 12 (V3), and 24 (V4) weeks after the intervention. The primary outcome measure was response rate at V3, with a positive response being defined as at least a 2-point increase in the Physicians' Rating Scale (PRS) score. The non-inferiority margin was set as -20% for the difference in the response rate. The secondary outcome measures included PRS score, passive range of motion (PROM) of the ankle and knee, and Gross Motor Function Measure 88 (GMFM-88). Any adverse events were investigated for safety implications.
The response rate of the Neuronox group at V3 was not inferior to that of the BOTOX group (90% lower limit=-11.58%). There were significant improvements in PRS, PROM of ankle dorsiflexion, and GMFM scores at V2, V3, and V4 in both groups. The changes in PRS score were not statistically different between the two groups in serial evaluation (p=0.96). PROM of the ankle dorsiflexion increased without any significant difference between the two groups, either overall (p=0.56) or at each visit (V2, p=0.32; V3, p=0.66; V4, p=0.90). The increase in GMFM score in serial measurements were not significantly different between the two groups (p=0.16), whereas it was larger in the BOTOX group than in the Neuronox group at V2 and V4 (p=0.03 and 0.05 respectively). The frequency of adverse events was not significantly different between the two groups (p=0.97), and drug-related complications of Neuronox treatment were not addressed.
The outcomes of Neuronox, based on PRS, proved to be as effective and safe as those of BOTOX for the treatment of spasticity in individuals with cerebral palsy.
本研究旨在评估一种新制造的肉毒毒素（Neuronox）与 BOTOX 相比，用于治疗脑瘫患儿痉挛性马蹄内翻足的疗效和安全性。
本研究为一项双盲、随机、对照试验，共纳入了 127 名 2-10 岁、因痉挛性马蹄内翻足就诊于 3 所大学附属医院的脑瘫患儿。对 119 名符合条件的参与者（平均年龄 4.33 岁，标准差 2.07 岁；76 名男性，43 名女性；79 名四肢瘫，40 名偏瘫）进行了评估，以确定其是否符合入选标准。其中 57 名参与者被归类为粗大运动功能分级系统（GMFCS）I 级，29 名参与者为 II 级，33 名参与者为 III 级。参与者被随机分配接受 Neuronox（n=60）或 BOTOX（n=59）小腿肌肉注射，偏瘫患儿剂量为 4U/kg，四肢瘫患儿剂量为 6U/kg。在干预后 4（V2）、12（V3）和 24（V4）周进行评估。主要结局指标为 V3 时的反应率，定义为医生评定量表（PRS）评分至少增加 2 分为阳性反应。非劣效性边界设定为反应率差异的-20%。次要结局指标包括 PRS 评分、踝关节和膝关节的被动活动度（PROM）以及粗大运动功能测量 88 分（GMFM-88）。对任何不良事件进行了安全性评估。
Neuronox 组在 V3 时的反应率不劣于 BOTOX 组（90%下限=-11.58%）。两组在 V2、V3 和 V4 时 PRS、踝关节背屈 PROM 和 GMFM-88 评分均有显著改善。两组在连续评估时 PRS 评分的变化无统计学差异（p=0.96）。踝关节背屈 PROM 无显著差异（总体：p=0.56；每次就诊：V2：p=0.32；V3：p=0.66；V4：p=0.90）。两组在 GMFM-88 评分的变化也无显著差异（p=0.16），但 BOTOX 组在 V2 和 V4 时的 GMFM-88 评分增加大于 Neuronox 组（p=0.03 和 0.05）。两组不良事件的发生频率无显著差异（p=0.97），且未出现与药物相关的 Neuronox 治疗并发症。
基于 PRS 的 Neuronox 治疗脑瘫患儿痉挛的疗效和安全性与 BOTOX 相当。
