Efficacy and safety of botulinum toxin type A for upper limb spasticity after stroke or traumatic brain injury: a systematic review with meta-analysis and trial sequential analysis.

Abstract

Muscle spasticity is a positive symptom after stroke and traumatic brain injury. Botulinum toxin type A (BoNT-A) injection is widely used for treating post stroke and traumatic brain injury spasticity. This study aimed to evaluate efficacy and safety of BoNT-A for upper limb spasticity after stroke and traumatic brain injury and investigate reliability and conclusiveness of available evidence for BoNT-A intervention. We searched electronic databases from inception to September 10 of 2016. Randomized controlled trials comparing the effectiveness between BoNT-A and placebo in stroke or traumatic brain injury adults with upper limb spasticity were included. Reliability and conclusiveness of the available evidence were examined with trial sequential analysis. From 489 citations identified, 22 studies were included, reporting results for 1804 participants. A statistically significant decrease of muscle tone was observed at each time point after BoNT-A injection compared to placebo (SMD at week 4=-0.98, 95% CI: -1.28 to -0.68; I2=66%, P=0.004; SMD at week 6=-0.85, 95% CI: -1.11 to -0.59, I2=1.2%, P=0.409; SMD at week 8=-0.87, 95% CI: -1.15 to -0.6, I2=0%, P=0.713; SMD at week 12=-0.67, 95% CI: -0.88 to -0.46, I2=0%, P=0.896; and SMD over week 12=-0.73, 95% CI: -1.21 to -0.24, I2=63.5%, P=0.065).Trial sequential analysis showed that as of year 2004 sufficient evidence had been accrued to show significant benefit of BoNT-A four weeks after injection over placebo control. BoNT-A treatment also significantly reduced Disability Assessment Scale Score than placebo at 4, 6 and 12-week follow-up period (WMD=-0.33, 95% CI: -0.63 to -0.03, I2=60%, P=0.114; WMD=-0.54, 95% CI: -0.74 to -0.33, I2= 0%, P=0.596 and WMD=-0.3, 95% CI: -0.45 to -0.14, I2=0%, P=0.426 respectively), and significantly increased patients' global assessment score at week 4 and 6 after injection (SMD=0.56, 95% CI: 0.28 to 0.83; I2=0%, P=0.681 and SMD=1.11, 95% CI: 0.4 to 1.77; I2=72.8%, P=0.025 respectively). No statistical difference was observed in the frequency of adverse events between BoNT-A and placebo group (RR=1.36, 95% CI [0.82, 2.27]; I2=0%, P=0.619). As compared with placebo, BoNT-A injections have beneficial effects with improved muscle tone and well-tolerated treatment for patients with upper limb spasticity post stroke or traumatic brain injury.