Objective: To evaluate the efficacy and safety of one-time injections of botulinum toxin type A (BoNTA) in Japanese patients with post-stroke upper limb spasticity.
Research design and methods: In a multicentre, randomised, double-blind, parallel-group, placebo-controlled study, 109 patients with upper limb spasticity were randomised to receive a single treatment with lower-dose (120-150 U) or higher-dose (200-240 U) BoNTA or placebo into upper limb muscles.
Clinical trial registration: NCT00460564.
Main outcome measures: The tone of the wrist flexor was assessed at baseline and at weeks 0, 1, 4, 6, 8 and 12 using the Modified Ashworth Scale (MAS) for wrist, finger, thumb and disability in activities of daily living (ADL) was rated using the 4-point Disability Assessment Scale (DAS). The primary endpoint was area under the curve (AUC) of the change from baseline in the MAS wrist score in the higher-dose groups.
Results: Subjects were randomised with 51 in the higher BoNTA group, 26 in the higher-dose placebo group, 21 in the lower BoNTA group and 11 in the lower-dose placebo group. Significant improvement in spasticity with higher-dose BoNTA was demonstrated by a mean difference in the AUC of the change from baseline in the MAS wrist score between the higher-dose BoNTA group and the higher-dose placebo group of -6.830 (p < 0.001, t-test), no significant different was demonstrated between the lower-dose BoNTA group and the lower-dose placebo group (p = 0.215, t-test). Significant improvements with higher-dose BoNTA were also observed in the DAS scores for limb position (p = 0.001-0.022) at all time points and dressing (p = 0.018-0.038, Wilcoxon test) at weeks 6, 8 and 12. No clinically relevant difference was noted in the frequency of treatment-related adverse events between BoNTA-treated and placebo-treated patients. The long-term efficacy and safety, and the effects on rehabilitation of BoNTA on upper limb will be evaluated using the data obtained in the open-label phase.
Conclusions: Higher-dose BoNTA reduced spasticity in upper limb muscles and improved ADL performance in terms of limb position and dressing. BoNTA is safe and effective in the treatment of post-stroke upper limb spasticity.