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. 2016 Oct 26;10(10):CD004314.
doi: 10.1002/14651858.CD004314.pub3.

Botulinum toxin type A versus botulinum toxin type B for cervical dystonia

Gonçalo S Duarte #  1 , Mafalda Castelão #, Filipe B Rodrigues #, Raquel E Marques #, Joaquim Ferreira, Cristina Sampaio, Austen P Moore, João Costa
Affiliations

Botulinum toxin type A versus botulinum toxin type B for cervical dystonia

Gonçalo S Duarte et al. Cochrane Database Syst Rev. .

Abstract

Background: 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.

Objectives: To compare the efficacy, safety and tolerability of botulinum toxin type A (BtA) versus botulinum toxin type B (BtB) in people with cervical dystonia.

Search methods: 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.

Selection criteria: Double-blind, parallel, randomised, placebo-controlled trials (RCTs) comparing BtA versus BtB in adults with cervical dystonia.

Data collection and analysis: 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.

Main results: 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.

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Conflict of interest statement

Costa J, Ferreira JJ, and Sampaio C were investigators in clinical trials in botulinum toxin A and B use in dystonia sponsored by Elan (manufacturer of BtB), Allergan (manufacturer of BtA), and Ipsen (manufacturer of BtA). Searching for studies, selection of studies, data extraction and analysis (including risk of bias), and GRADE assessment were performed by authors (FRB, GSD, MC, REM) that are not trialists. Ferreira JJ and Sampaio C were speakers in symposiums promoted by Elan, Allergan, and Ipsen. Moore AP has received royalties from Ipsen for the use 'LIVEchart' scoring system for botulinum toxin treatment efficacy. He has additionally received consulting fees from Ipsen, Merz (manufacturer of BtA), Eisai (manufacturer of BtB), and Allergan. The same companies have provided for support for travel to meetings for studies or other purposes.

Figures

1
1
BtA vs BtB in Cervical Dystonia Flow Diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Botulinum toxin type A versus botulinum toxin type B, outcome: 1.1 Overall cervical dystonia improvement as assessed with validated scales: change from baseline to week 4.
1.1
1.1. Analysis
Comparison 1 Botulinum toxin type A versus botulinum toxin type B, Outcome 1 Overall cervical dystonia improvement as assessed with validated scales: change from baseline to week 4.
1.2
1.2. Analysis
Comparison 1 Botulinum toxin type A versus botulinum toxin type B, Outcome 2 Cervical dystonia associated severity: change from baseline to week 2‐4 as assessed with validated scales.
1.3
1.3. Analysis
Comparison 1 Botulinum toxin type A versus botulinum toxin type B, Outcome 3 Cervical dystonia associated disability: change from baseline to week 2‐4 as assessed with validated scales.
1.4
1.4. Analysis
Comparison 1 Botulinum toxin type A versus botulinum toxin type B, Outcome 4 Proportion of participants with adverse events.
1.5
1.5. Analysis
Comparison 1 Botulinum toxin type A versus botulinum toxin type B, Outcome 5 Subjective change as assessed by the patient at week 4.
1.6
1.6. Analysis
Comparison 1 Botulinum toxin type A versus botulinum toxin type B, Outcome 6 Subjective change as assessed by clinician at week 4.
1.7
1.7. Analysis
Comparison 1 Botulinum toxin type A versus botulinum toxin type B, Outcome 7 Cervical dystonia associated pain: change from baseline to week 2‐4 as assessed with validated scales.
1.8
1.8. Analysis
Comparison 1 Botulinum toxin type A versus botulinum toxin type B, Outcome 8 Adverse event: sore throat/dry mouth.
1.9
1.9. Analysis
Comparison 1 Botulinum toxin type A versus botulinum toxin type B, Outcome 9 Adverse event: dysphagia.
1.10
1.10. Analysis
Comparison 1 Botulinum toxin type A versus botulinum toxin type B, Outcome 10 Adverse event: injection site pain.
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Update of

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References to other published versions of this review

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