Duarte Gonçalo S, Castelão Mafalda, Rodrigues Filipe B, Marques Raquel E, Ferreira Joaquim, Sampaio Cristina, Moore Austen P, Costa João
Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, Lisboa, Lisboa, Portugal, 1649-028.
Cochrane Database Syst Rev. 2016 Oct 26;10(10):CD004314. doi: 10.1002/14651858.CD004314.pub3.
This is an update of a Cochrane review first published in 2003. Cervical dystonia is the most common form of focal dystonia and is a disabling disorder characterised by painful involuntary head posturing. There are two available formulations of botulinum toxin, with botulinum toxin type A (BtA) usually considered the first line therapy for this condition. Botulinum toxin type B (BtB) is an alternative option, with no compelling theoretical reason why it might not be as- or even more effective - than BtA.
To compare the efficacy, safety and tolerability of botulinum toxin type A (BtA) versus botulinum toxin type B (BtB) in people with cervical dystonia.
To identify studies for this review we searched the Cochrane Movement Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, reference lists of articles and conference proceedings. All elements of the search, with no language restrictions, were last run in October 2016.
Double-blind, parallel, randomised, placebo-controlled trials (RCTs) comparing BtA versus BtB in adults with cervical dystonia.
Two independent authors assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third author. We performed meta-analyses using the random-effects model, for the comparison BtA versus BtB to estimate pooled effects and corresponding 95% confidence intervals (95% CI). No prespecified subgroup analyses were carried out. The primary efficacy outcome was improvement on any validated symptomatic rating scale, and the primary safety outcome was the proportion of participants with adverse events.
We included three RCTs, all new to this update, of very low to low methodological quality, with a total of 270 participants.Two studies exclusively enrolled participants with a known positive response to BtA treatment. This raises concerns of population enrichment, with a higher probability of benefit from BtA treatment. None of the trials were free of for-profit bias, nor did they provide information regarding registered study protocols. All trials evaluated the effect of a single Bt treatment session, and not repeated treatment sessions, using doses from 100 U to 250 U of BtA (all onabotulinumtoxinA, or Botox, formulations) and 5000 U to 10,000 U of BtB (rimabotulinumtoxinB, or Myobloc/Neurobloc).We found no difference between the two types of botulinum toxin in terms of overall efficacy, with a mean difference of -1.44 (95% CI -3.58 to 0.70) points lower on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) for BtB-treated participants, measured at two to four weeks after injection. The proportion of participants with adverse events was also not different between BtA and BtB (BtB versus BtA risk ratio (RR) 1.40; 95% CI 1.00 to 1.96). However, when compared to BtA, treatment with BtB was associated with an increased risk of one adverse events of special interest, namely treatment-related sore throat/dry mouth (BtB versus BtA RR of 4.39; 95% CI 2.43 to 7.91). Treatment-related dysphagia (swallowing difficulties) was not different between BtA and BtB (RR 2.89; 95% CI 0.80 to 10.41). The two types of botulinum toxin were otherwise clinically non-distinguishable in all the remaining outcomes.
AUTHORS' CONCLUSIONS: The previous version of this review did not include any trials, since these were still ongoing at the time. Therefore, with this update we are able to change the conclusions of this review. There is low quality evidence that a single treatment session of BtA (specifically onabotulinumtoxinA) and a single treatment session of BtB (rimabotulinumtoxinB) are equally effective and safe in the treatment of adults with certain types of cervical dystonia. Treatment with BtB appears to present an increased risk of sore throat/dry mouth, compared to BtA. Overall, there is no clinical evidence from these single-treatment trials to support or contest the preferential use of one form of botulinum toxin over the other.
这是对2003年首次发表的Cochrane综述的更新。颈部肌张力障碍是局限性肌张力障碍最常见的形式，是一种致残性疾病，其特征为头部疼痛性不自主姿势。有两种肉毒毒素制剂，其中A型肉毒毒素（BtA）通常被认为是这种疾病的一线治疗方法。B型肉毒毒素（BtB）是一种替代选择，理论上并无令人信服的理由表明其效果不如BtA，甚至可能更有效。
比较A型肉毒毒素（BtA）与B型肉毒毒素（BtB）治疗颈部肌张力障碍患者的疗效、安全性和耐受性。
为了识别本综述的研究，我们检索了Cochrane运动障碍组试验注册库、Cochrane对照试验中央注册库（CENTRAL）、MEDLINE、Embase、文章参考文献列表和会议论文集。检索的所有内容均无语言限制，最后一次检索于2016年10月进行。
比较BtA与BtB治疗成年颈部肌张力障碍患者的双盲、平行、随机、安慰剂对照试验（RCT）。
两位独立作者评估记录、选择纳入研究、使用纸质表格提取数据，并评估偏倚风险。我们通过协商一致或咨询第三位作者解决分歧。我们使用随机效应模型进行荟萃分析，比较BtA与BtB，以估计合并效应和相应的95%置信区间（95%CI）。未进行预先指定的亚组分析。主要疗效结局是在任何经过验证的症状评分量表上的改善，主要安全性结局是发生不良事件的参与者比例。
我们纳入了三项RCT，均为本更新中的新研究，方法学质量非常低到低，共有270名参与者。两项研究专门纳入了已知对BtA治疗有阳性反应的参与者。这引发了对人群富集的担忧，即从BtA治疗中获益的可能性更高。所有试验均存在商业利益偏倚，且均未提供有关注册研究方案的信息。所有试验均评估了单次肉毒毒素治疗的效果，而非重复治疗，使用的BtA剂量为100U至250U（均为注射用A型肉毒毒素，即保妥适制剂），BtB剂量为5000U至10000U（利司扑兰肉毒毒素B，即Myobloc/Neurobloc）。我们发现两种肉毒毒素在总体疗效方面无差异，在注射后两至四周测量，接受BtB治疗的参与者在多伦多西部痉挛性斜颈评分量表（TWSTRS）上的平均得分比接受BtA治疗的参与者低1.44分（95%CI -3.58至0.70）。BtA和BtB发生不良事件的参与者比例也无差异（BtB与BtA的风险比（RR）为1.40；95%CI 1.00至1.96）。然而，与BtA相比，BtB治疗与一种特殊不良事件的风险增加相关，即治疗相关的喉咙痛/口干（BtB与BtA的RR为4.39；95%CI 2.43至7.91）。治疗相关的吞咽困难在BtA和BtB之间无差异（RR 2.89；95%CI 0.80至10.41）。在所有其他结局方面，两种肉毒毒素在临床上无明显差异。
本综述的上一版本未纳入任何试验，因为当时这些试验仍在进行中。因此，通过本次更新，我们能够改变本综述的结论。有低质量证据表明，单次使用BtA（特别是注射用A型肉毒毒素）和单次使用BtB（利司扑兰肉毒毒素B）治疗某些类型的成年颈部肌张力障碍患者同样有效且安全。与BtA相比，BtB治疗似乎增加了喉咙痛/口干的风险。总体而言，这些单治疗试验中没有临床证据支持或反对优先使用一种肉毒毒素而非另一种。
