Botulinum toxin type A in post-stroke upper limb spasticity

Abstract

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.

Key words:

• Botulinum toxin type A
• Disability Assessment Scale
• Modified Ashworth Scale
• Spasticity
• Upper limb

Transparency

Declaration of funding

This study was sponsored by GlaxoSmithKline K.K.

Declaration of financial/other relationships

R.K. has disclosed that he has served on the steering committee of the GSK1358820 Spasticity Study and received grants from GlaxoSmithKline K.K. He has also disclosed that he receives honoraria for speaker's bureau activities from Eisai Co. Ltd.

Y.O., K.S., T.M., Y.U. and M.I. have disclosed that they are employees of GlaxoSmithKline K.K.

Acknowledgements

The authors thank the investigators of GSK1358820 Spasticity Study Group who enrolled their patients into this study: M Abo, The Jikei University School of Medicine, Tokyo; H Chagawa, Iwakuni Medical Center, Yamaguchi; K Fukuyama, Fukuoka Wajiro Hospital, Fukuoka; Y Igarashi, Aida Kinen Rehabilitation Hospital, Ibaraki; H Inada, Nakaizu Rehabilitation Center, Shizuoka; K Oka, Oka Neurocare Clinic, Shizuoka; T Nagayama, Tsurumaki Onsen Hospital, Kanagawa; H Ito, Mifukai Vihara Hananosato Hospital, Hiroshima; T Kamei, Chigasaki Tokushukai Medical Center, Kanagawa; F Kasai, Showa University Fujigaoka Rehabilitation Hospital, Kanagawa; J Kawada, Shonan Kamakura General Hospital, Kanagawa; N Kawate, Showa University Hospital, Tokyo; A Kimura, Keio University Tsukigase Rehabilitation Center, Shizuoka; K Matsunaga, Kumamoto Kinoh Hospital, Kumamoto; M Mizuma, Showa University Hospital, Tokyo; T Ogasawara, Minami-Sapporo Neurosurgical Clinic, Hokkaido; S Oota, Brain Attack Center Oota Memorial Hospital, Hiroshima; T Shimizu, Sapporo Shuyukai Hospital, Hokkaido; R Takeda, Nakamura Memorial South Hospital, Hokkaido; S Yura, Tomakomai Nissho Hospital, Hokkaido. The authors also thank all the participating patients for their time and efforts.