Kaji Ryuji, Shimizu Hiroki, Takase Takao, Osawa Mikio, Yanagisawa Nobuo
Department of Clinical Neuroscience, Tokushima University Graduate School, Japan.
Brain Nerve. 2013 Feb;65(2):203-11.
We conducted a single-dose, placebo-controlled, double-blind, dose-response study of NerBloc®(rimabotulinumtoxinB) in patients with cervical dystonia (placebo, 2,500 U, 5,000 U, 10,000 U). The primary endpoint, the change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-total score at 4 weeks post dose from baseline, showed a significant improvement in all treatment groups (2,500 U, 5,000 U, 10,000 U) compared with the placebo group. As for the secondary endpoints, the change of TWSTRS subscales, severity, disability and pain scores, at 4 weeks post dose in 10,000 U group, showed a significant improvement compared with the placebo group, however, no significant differences were observed between 2,500 U or 5,000 U and placebo group. The subject's and physician's global assessments (visual analog scale; VAS) at 4 weeks post dose also showed significant improvement in all treatment groups relative to the placebo group, whereas subject's pain assessment (VAS) at 4 weeks post dose did not show significant improvement in any of treatment groups. The incidence rate of adverse events was not substantially different between the placebo group and 2,500 or 5,000 U group, but significantly higher in 10,000 U group than in the placebo group. Adverse events frequently observed in active drug groups included dry mouth/thirst and dysphagia, all of which were mild in severity. There were no adverse events that led to death, serious disorders or study discontinuations. The incidence rate of abnormal laboratory values did not show significant difference in any of parameters between the placebo group and any of treatment groups. NerBloc® possessing muscle relaxing effect is expected to be a potential treatment to improve symptoms of cervical dystonia. Clinically recommended dose will range from 2,500 U to 10,000 U. In this study, 10,000 U group was the most effective and the effect lasted the longest. The efficacy and safety profile of NerBloc ® in this study was similar to that in AN072-009 study conducted in the US.
我们开展了一项针对颈部肌张力障碍患者的单剂量、安慰剂对照、双盲、剂量反应研究，研究药物为NerBloc®（利美布托毒素B）（安慰剂、2500单位、5000单位、10000单位）。主要终点为给药后4周时多伦多西部痉挛性斜颈评定量表（TWSTRS）总分相对于基线的变化，结果显示所有治疗组（2500单位、5000单位、10000单位）与安慰剂组相比均有显著改善。至于次要终点，10000单位组给药后4周时TWSTRS分量表、严重程度、残疾和疼痛评分的变化与安慰剂组相比有显著改善，然而，2500单位或5000单位组与安慰剂组之间未观察到显著差异。给药后4周时受试者和医生的整体评估（视觉模拟量表；VAS）相对于安慰剂组在所有治疗组中也显示出显著改善，而给药后4周时受试者的疼痛评估（VAS）在任何治疗组中均未显示出显著改善。安慰剂组与2500单位或5000单位组之间不良事件的发生率没有实质性差异，但10000单位组显著高于安慰剂组。在活性药物组中经常观察到的不良事件包括口干/口渴和吞咽困难，所有这些不良事件的严重程度均为轻度。没有导致死亡、严重疾病或研究中断的不良事件。安慰剂组与任何治疗组之间在任何参数上实验室值异常的发生率均未显示出显著差异。具有肌肉松弛作用的NerBloc®有望成为改善颈部肌张力障碍症状的潜在治疗方法。临床推荐剂量范围为2500单位至10000单位。在本研究中，10000单位组最有效且效果持续时间最长。本研究中NerBloc®的疗效和安全性概况与在美国进行的AN072 - 009研究相似。
