Botulinum toxin type B for cervical dystonia.
Botulinum toxin type B for cervical dystonia.
复制标题
B 型肉毒毒素治疗颈肌张力障碍。
DOI：
10.1002/14651858.cd004315
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
C. Sampaio
中科院分区：
文献类型：
--
作者：
J. Costa;C. Espírito‐Santo;A. A. Borges;J. Ferreira;M. Coelho;Peter Moore;C. Sampaio
背景
颈部肌张力障碍是局灶性肌张力障碍的最常见形式。它的特点是头部不自主的姿势，并且经常与颈部疼痛相关。残疾和社交退缩很常见。大多数颈肌张力障碍病例是特发性的，通常是一种终生疾病。近年来，A型肉毒杆菌毒素（BtA）已成为一线疗法。然而，一些患者对其产生耐药性。这个问题引发了对另一种肉毒杆菌毒素 (Bt) 血清型 Bt 型 B (BtB) 的研究，以解决 BtB 治疗颈肌张力障碍的临床疗效、效应大小和安全性问题。
目标
确定肉毒杆菌毒素（BtB）是否是治疗颈肌张力障碍的有效且安全的方法。
搜寻策略
我们使用 Cochrane 运动障碍组试验注册库、Cochrane 对照试验中央注册库 (CENTRAL)、MEDLINE、EMBASE 确定了纳入综述的研究；手工检索《运动障碍杂志》以及有关运动障碍和肉毒杆菌毒素的国际会议摘要，通过与该领域的其他研究人员交流，通过搜索使用上述搜索策略找到的论文参考文献列表，以及通过联系作者和药品制造商。
选择标准
如果研究在随机、安慰剂对照试验中评估了 BtB 治疗颈部肌张力障碍的功效，我们认为这些研究有资格纳入本次审查。
数据收集和分析
我们使用论文形式从纳入的研究中收集数据，并由两名独立评审员进行双重提取。两位评审员评估了每项试验的内部有效性，并通过讨论解决了分歧。使用的结果指标包括不良事件、症状评分量表的改善、患者和临床医生的主观评价、疼痛评分的变化、生活质量评估的变化。
主要结果
研究是短期（16 周），采用单次 BtB 注射。所有研究都是多中心的，并在美国进行。所有患者之前均接受过 BtA 治疗。这些试验在患者是否仍对 BtA 有反应方面存在差异，但其他入选标准相似。所有研究均在一组中使用 10,000 单位的 BtB 剂量，且给药技术相同。对招募 308 名参与者的三项试验进行的荟萃分析显示，第四周时多伦多西部痉挛性斜颈评定量表 (TWSTRS) 总分在统计学和临床上均显着改善，改善至少 20% 的患者数量的 Peto 比值比 (OR) 为 4.69（95% CI 2.06 至 10.69），加权平均差为 -5.92（95% CI） -9.61 至 -2.23）。主观评分量表（患者总体变化评估、研究者总体变化评估和患者模拟疼痛评估）也有所改善。与 BtB 作用机制明显相关的不良事件包括吞咽困难和口干，并且 BtB 治疗组中发生任何不良事件的患者数量更为频繁。亚组分析显示，主观和客观获益、不良事件发生频率和严重程度均存在明确的剂量反应关系，并且在主要结局中，BtA 耐药患者比 BtA 应答者获益更大。效果持续时间约为16周。我们发现三项符合条件的研究招募了 308 名参与者。研究是短期（16 周），采用单次 BtB 注射。所有研究都是多中心的，并在美国进行。所有患者之前均接受过 BtA 治疗。这些试验在患者是否仍对 BtA 有反应方面存在差异，但其他入选标准相似。患者组经过适当选择并且匹配良好。从方法学的角度来看，这些试验可能没有受到重要的选择、性能或损耗偏倚的影响，并且所有研究都使用了意向治疗分析。尽管所有研究在一组中使用了 10,000 单位的 BtB 并且给药技术相同，但研究之间的剂量差异很大。所有试验的主要结果是第四周时 TSTRRS 总分的变化，并且研究之间的其他疗效结果相似。所有试验中退出的人数很少且平衡。并给出了退出的理由。一项随机双盲安慰剂对照研究被排除，因为无法提取结果数据。荟萃分析显示，第四周时 TWSTRS 总分 Peto 比值比 (OR) 为 20%（OR 4.69；95% CI 2.06 至 10.69），加权平均差为 -5.92（95% CI -9.61 至 -2.23），具有统计学和临床显着改善。主观评分量表（患者总体变化评估、研究者总体变化评估和患者模拟疼痛评估）也有所改善。这些主观量表变化的加权平均差异在-13% 到-21% 之间变化。然而，对于许多结果，我们无法合并所有研究的数据。只有与 BtB 作用机制明显相关的不良事件在治疗组中更为频繁。这些包括吞咽困难和口干。 BtB 组出现任何不良事件的患者数量更为频繁。亚组分析显示主观和客观获益以及不良事件的频率和严重程度存在明确的剂量反应关系。亚组分析显示，在主要结局中，BtA 耐药患者比 BtA 应答者获益更大。效果持续时间约为16周。这些试验没有测量生活质量，也没有确定效果或免疫原性的长期持续时间
作者的结论
单次注射 BtB 治疗颈肌张力障碍是有效且安全的。长期非对照研究表明，进一步的注射周期对大多数患者仍然有效。未来的研究应探索技术因素，例如最佳治疗间隔以及使用图像或肌电图指导进行给药。其他问题包括服务提供、生活质量、长期疗效和安全性，以及 BtA、BtB 和其他治疗（如深部脑刺激）的相关适应症。
BACKGROUND
Cervical dystonia is the most common form of focal dystonia. It is characterized by involuntary posturing of the head and frequently is associated with neck pain. Disability and social withdrawal are common. Most cases of cervical dystonia are idiopathic and generally it is a life-long disorder. In recent years, Botulinum toxin type A (BtA) has become the first line therapy. However, some patients become resistant to it. This problem led to the study of another Botulinum toxin (Bt) serotype, Bt type B (BtB) to address the issues of clinical efficacy, effect size, and safety of BtB in the treatment of cervical dystonia.
OBJECTIVES
To determine whether botulinum toxin (BtB) is an effective and safe treatment for cervical dystonia.
SEARCH STRATEGY
We identified studies for inclusion in the review using the Cochrane Movement Disorders Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE; and by handsearching the Movement Disorders Journal and abstracts of international congresses on movement disorders and botulinum toxin, by communication with other researchers in the field, by searching reference lists of papers found using the above search strategies, and by contacting authors and drug manufacturers.
SELECTION CRITERIA
We considered studies eligible for inclusion in the review if they evaluated the efficacy of BtB for the treatment of cervical dystonia in randomized, placebo-controlled trials.
DATA COLLECTION AND ANALYSIS
We used a paper pro forma to collect data from the included studies with double extraction by two independent reviewers. Both reviewers assessed each trial for internal validity and settled differences by discussion. The outcome measures used included adverse events, improvement in symptomatic rating scales, subjective evaluation by patients and clinicians, changes in pain scores, changes in quality of life assessments.
MAIN RESULTS
Studies were short term (16 weeks) employing a single BtB injection session. All were multicentre and conducted in the US. All patients included had previously received BtA. The trials differed with respect to whether or not the patients were still responding to BtA but other entry criteria were similar. All studies used a dose of 10,000 Units of BtB in one group and the technique of administration was the same. Meta-analysis of three trials enrolling 308 participants showed statistically and clinically significant improvements in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at week four with a Peto odds ratio (OR) for the number of patients who had at least a 20% improvement of 4.69 (95% CI 2.06 to 10.69) and a weighted mean difference of -5.92 (95% CI -9.61 to -2.23). Subjective rating scales (Patient Global Assessment of Change, Investigator Global Assessment of Change, and Patient Analog Pain Assessment) also improved. Adverse events clearly associated with the mechanism of action of BtB included dysphagia and dry mouth and the number of patients with any adverse event were more frequent in BtB treatment groups. Subgroup analyses showed a clear dose-response relationship for subjective and objective benefit, for frequency and severity of adverse events, and a greater benefit for BtA resistant patients than BtA responders in the primary outcome. The duration of effect was about 16 weeks. We found three eligible studies enrolling 308 participants. Studies were short term (16 weeks) employing a single BtB injection session. All were multicentre and conducted in the US. All patients included had previously received BtA. The trials differed with respect to whether or not the patients were still responding to BtA but other entry criteria were similar. Patient groups were appropriately selected and well matched. From the methodological point of view these trials were probably not subjected to important selection, performance or attrition bias and all studies used an intention-to-treat analysis.The dose varied significantly between studies although all used 10,000 Units of BtB in one group and the technique of administration was the same. The primary outcome in all trials was change in TWSTRS total score at week four and other efficacy outcomes were similar between studies. The number of dropouts was small and balanced in all trials. Reasons for withdrawals were given. One randomized double-blind placebo-controlled study was excluded because data couldn't be extracted for the outcomes. Meta-analysis showed statistically and clinically significant improvements with a Peto odds ratio (OR) of 20% in TWSTRS total score at week four (OR 4.69; 95% CI 2.06 to 10.69) and a weighted mean difference of -5.92 (95% CI -9.61 to -2.23). Subjective rating scales (Patient Global Assessment of Change, Investigator Global Assessment of Change, and Patient Analog Pain Assessment) also improved. The weighted mean difference for changes in these subjective scales varied between -13% to -21%. However, for many of the outcomes, we could not combine data from all studies. Only adverse events clearly associated with the mechanism of action of BtB were more frequent in the treatment group. These included dysphagia and dry mouth. The number of patients with any adverse event was more frequent with BtB. Subgroup analyses showed a clear dose-response relationship for subjective and objective benefit and for frequency and severity of adverse events. Subgroup analyses showed a greater benefit for the BtA resistant patients than BtA responders in the primary outcome. The duration of effect was about 16 weeks. These trials did not measure quality of life nor did they establish the long term duration of effect or immunogenicity
AUTHORS' CONCLUSIONS
A single injection of BtB was effective and safe for treating cervical dystonia. Long-term uncontrolled studies suggested that further injection cycles continue to work for most patients. Future research should explore technical factors such as the optimum treatment intervals and use of image or electromyographic guidance for administration. Other issues include service delivery, quality of life, long-term efficacy and safety, and the relative indications for BtA, BtB and other treatments such as deep brain stimulation.