Background: This is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia and is a highly disabling movement disorder characterised by involuntary, usually painful, head posturing. Currently, botulinum toxin type A (BtA) is considered the first line therapy for this condition.
Objectives: To compare the efficacy, safety, and tolerability of botulinum toxin type A (BtA) versus placebo in people with cervical dystonia.
Search methods: To identify studies for this review we searched Cochrane Movement Disorders' Trials Register, CENTRAL, MEDLINE, Embase, reference lists of articles and conference proceedings. All elements of the search, with no language restrictions, were run in October 2016.
Selection criteria: Double-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtA versus placebo in adults with cervical dystonia.
Data collection and analysis: Two review authors independently 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 review author. We performed meta-analyses using a random-effects model for the comparison of BtA versus placebo to estimate pooled effects and corresponding 95% confidence intervals (95% CI). In addition, we performed preplanned subgroup analyses according to BtA dose used, the BtA formulation used, and the use or not of guidance for BtA injection. The primary efficacy outcome was improvement in cervical dystonia-specific impairment. The primary safety outcome was the proportion of participants with any adverse event.
Main results: We included eight RCTs of moderate overall risk of bias, including 1010 participants with cervical dystonia. Six studies excluded participants with poorer responses to BtA treatment, therefore including an enriched population with a higher probability of benefiting from this therapy. Only one trial was independently funded. All RCTs evaluated the effect of a single BtA treatment session, using doses from 150 U to 236 U of onabotulinumtoxinA (Botox), 120 U to 240 U of incobotulinumtoxinA (Xeomin), and 250 U to 1000 U of abobotulinumtoxinA (Dysport).BtA was associated with a moderate-to-large improvement in the participant's baseline clinical status as assessed by investigators, with reduction of 8.06 points in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS total score) at week 4 after injection (95% CI 6.08 to 10.05; I2 = 0%) compared to placebo, corresponding on average to a 18.7% improvement from baseline. The mean difference (MD) in TWSTRS pain subscore at week 4 was 2.11 (95% CI 1.38 to 2.83; I2 = 0%). Overall, both participants and clinicians reported an improvement of subjective clinical status. There were no differences between groups regarding withdrawals due to adverse events. However, BtA treatment was associated with an increased risk of experiencing an adverse event (risk ratio (RR) 1.19; 95% CI 1.03 to 1.36; I2 = 16%). Dysphagia (9%) and diffuse weakness/tiredness (10%) were the most common treatment-related adverse events (dysphagia: RR 3.04; 95% CI 1.68 to 5.50; I2 = 0%; diffuse weakness/tiredness: RR 1.78; 95% CI 1.08 to 2.94; I2 = 0%). Treatment with BtA was associated with a decreased risk of participants withdrawing from trials. We have moderate certainty in the evidence across all of the aforementioned outcomes.We found no evidence supporting the existence of a clear dose-response relationship with BtA, nor a difference between BtA formulations, nor a difference with use of EMG-guided injection.Due to clinical heterogeneity, we did not pool data regarding health-related quality of life, duration of clinical effect, or the development of secondary non-responsiveness.
Authors' conclusions: We have moderate certainty in the evidence that a single BtA treatment session is associated with a significant and clinically relevant reduction of cervical dystonia-specific impairment, including severity, disability, and pain, and that it is well tolerated, when compared with placebo. There is also moderate certainty in the evidence that people treated with BtA are at an increased risk of developing adverse events, most notably dysphagia and diffuse weakness. There are no data from RCTs evaluating the effectiveness and safety of repeated BtA injection cycles. There is no evidence from RCTs to allow us to draw definitive conclusions on the optimal treatment intervals and doses, usefulness of guidance techniques for injection, the impact on quality of life, or the duration of treatment effect.