Intervention Review

Botulinum toxin type B for cervical dystonia

  1. João Costa1,*,
  2. Cláudia C Espírito-Santo1,
  3. Ana A Borges1,
  4. Joaquim Ferreira1,
  5. Miguel M Coelho1,
  6. Peter Moore2,
  7. Cristina Sampaio1

Editorial Group: Cochrane Movement Disorders Group

Published Online: 18 OCT 2004

Assessed as up-to-date: 6 JUN 2004

DOI: 10.1002/14651858.CD004315.pub2


How to Cite

Costa J, Espírito-Santo CC, Borges AA, Ferreira J, Coelho MM, Moore P, Sampaio C. Botulinum toxin type B for cervical dystonia. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD004315. DOI: 10.1002/14651858.CD004315.pub2.

Author Information

  1. 1

    Faculdade de Medicina de Lisboa, Laboratório de Farmacologia Clínica e Terapêutica, Lisboa, Portugal

  2. 2

    NHS Trust, The Walton Centre for Neurology and Neurosurgery, Liverpool, UK

*João Costa, Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Lisboa, 1649-028, Portugal. joaoncosta@sapo.pt.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 18 OCT 2004

SEARCH

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

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 methods

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

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Botulinum toxin type B for cervical dystonia or involuntary positioning of the head

Cervical dystonia is the most common form of focal dystonia and is characterized by involuntary posturing of the head. It is frequently associated with neck pain and may lead to physical disability and social withdrawal. Botulinum toxin type A (BtA) has become the first line therapy but some patients become resistant to this drug. Another serotype of Botulum toxin, type B (BtB) has been developed. Three randomized controlled studies of a single intramuscular injection of BtB (up to a dose of 10,000 Units) showed improvements in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score, which includes measures of disability, severity and pain, and patient assessed measures four weeks after injection and lasting about 16 weeks, even in patients resistant to BtA. Adverse events associated with how the drug works included difficulty in swallowing (dysphagia) and dry mouth.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

以Botulinum toxin type B治療頸肌張力異常症

頸肌張力異常症是一種常見的局限性肌張力障礙。主要病徵是非自主性的頭部姿勢,且常和頸部疼痛有關。殘障和社交退縮是很常見的。大部分頸肌張力異常症都是原發性的,且通常是終身的異常。近幾年來,Botulinum toxin type A(BtA)已經成為第一線治療。然而,有些病患已經開始對其產生抗藥性。使大家開始研究Botulinum toxin (Bt)的另一個血清型,Bt type B(BtB)用於治療頸肌張力異常症的有效性、療效大小及安全性。

目標

評估botulinum toxin (BtB)對於頸肌張力異常症是否是一個有效且安全的治療方式。

搜尋策略

我們利用the Cochrane Movement Disorders Group trials register、the Cochrane Central Register of Controlled Trials (CENTRAL)、MEDLINE、EMBASE;手動搜尋the Movement Disorders Journal及關於運動障礙和botulinum toxin的國際會議摘要、和這個領域的研究者進行溝通、蒐尋找到論文中的參考資料以及和論文作者及藥物廠商連絡等方式,搜尋欲收錄的研究。

選擇標準

我們收錄有評估BtB治療頸肌張力異常症療效的隨機、安慰劑對照試驗。

資料收集與分析

我們由2位作者以二次擷取的方式,利用預先制定好的格式,從收錄的研究中收集數據。2位作者對每個試驗都要做內部確效評估,意見分歧的部分則經過討論取得共識。以不良反應、症狀改善量表、醫師和病患的主觀評估、疼痛分數的改變、生活品質的改變作為結果量測。

主要結論

研究都是短期的(16周),使用單一BtB注射。所有的研究都涉及多重機構,且是在美國執行。所有的病人在試驗前都是以BtA治療。各個試驗在病人是否對BtA有反應的標準不太一樣,但其他的收錄標準都很類似。所有的研究都使用10,000單位的BtB,且使用方式和技術都是相同的。包含3個試驗,總共308位病患的整合分析顯示,在治療第4周後,Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)的總分有統計上和臨床上顯著的改善,至少改善20%的病患數目的Peto odds ratio (OR)是4.69 (95% CI 2.06 to 10.69),加權並均差是−5.92 (95% CI −9.61 to −2.23)。主觀評分量表(Patient Global Assessment of Change、 Investigator Global Assessment of Change及Patient Analog Pain Assessment)也有改善。和BtB機轉相關的不良反應,包括吞嚥困難和口乾及發生不良反應的病患數,在使用BtB的組別比較多。子群組分析顯示主觀和客觀利益及不良反應的頻率和嚴重度,跟劑量有明顯相關,在主要結果上,有BtA抗藥性的病患比仍對BtA有反應的病患獲得更大的效果。效果的持續時間大約為16周。我們發現3個可用的研究,總共包和308位病患,研究都是短期的(16周),使用單一BtB注射。所有的研究都涉及多重機構,且是在美國執行。所有參與的病患都在之前接受過BtA治療。各個試驗在病人是否仍對BtA有反應的標準不太一樣,但其他的收錄標準都很類似。病人組別都被適當的篩選並配合。以方法的觀點來看,這些試驗沒受到重要選擇、實施或退出偏差的牽制,且所有的研究都是使用意圖治療分析。雖然都是使用10,000單位的BtB,且施予方式也相同,但各研究使用的劑量差異很大。所有試驗的主要結果都是以第4周TWSTRS總分的改變表示,各研究的其它療效結果種類也都很相似。退出試驗的人數很少,每個試驗都很平均。有列出退出試驗的原因。有1個隨機雙盲的安慰劑對照試驗被我們排除,因為無法從其結果中擷取數據。整合分析顯示,第四週的TWSTRS總分有統計和臨床上的顯著改善,Peto odds ratio (OR)為20%(OR4.69; 95% CI 2.06 to 10.69),加權平均差為−5.92 (95% CI −9.61 to −2.23)。主觀評分量表(Patient Global Assessment of Change, Investigator Global Assessment of Change及Patient Analog Pain Assessment)也有改善。這些主觀量表加權平均差的改變範圍從−13%到−21%。然而對於大部分的結果,我們無法合併所有研究的數據。在以BtB治療的組別較常發生和BtB機轉相關的不良反應。包括吞嚥困難及口乾。發生不良反應的人數在BtB的組別較多。子群組分析顯示主觀和客觀?處及不良反應的頻率和嚴重度,很明顯的和劑量有關。子群組分析顯示,在主要結果中,對BtA沒反應的病患比對BtA仍有反應的病患能從BtB治療獲得更多的好處。藥效大約持續16周。這些試驗沒有評估生活品質,也沒有評估長期的效果或免疫原性。

作者結論

對於治療頸肌張力異常,BtB的單一注射是有效且安全的。長期的非對照研究認為持續的注射循環對大多數病患是有用的。未來的研究應該討論技術因子,像是最佳治療間隔及用影像或肌電指數作為給藥的準則。其他議題包括服務的提供、生活品質、長期的療效和安全性及BtA、BtB和其他治療,例如深部腦刺激的相關指示。

翻譯人

本摘要由朱奕蓁翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

以Botulinum toxin type B治療頸肌張力異常症或頭部非自主運動。頸肌張力異常症是一種常見的局限性肌張力障礙,它的主要病徵是非自主性的頭部姿勢。通常和頸部疼痛有關且可能造成生理上的殘障及社交退縮。Botulinum toxin type A(BtA)目前是第一線治療,但有些病患已經開始產生抗藥性。現在已經研發出Botulinum toxin (Bt)的另一個血清型,Bt type B (BtB)。3個使用BtB單一肌肉注射(最高達每劑量10,000單位)的隨機試驗,顯示其能改善Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)的總分,包括注射4周後的殘障量表、嚴重度及疼痛量表,以及病患評估量表,療效大約可維持16周,就算是對BtA有抗藥性的病患也有效。和藥物機轉相關的不良反應有吞嚥困難及口乾。