Botulinum neurotoxin versus tizanidine in upper limb spasticity: a placebo-controlled study
- D M Simpson1,
- J M Gracies1,2,
- S A Yablon3,
- R Barbano4,
- A Brashear5,
- the BoNT/TZD Study Team
- 1The Mount Sinai School of Medicine, New York, New York, USA
- 2CHU Henri Mondor, Créteil, France
- 3University of Mississippi School of Medicine, Jackson, Mississippi, USA
- 4University of Rochester, New York, USA
- 5Wake Forest University School of Medicine, Winston Salem, North Carolina, USA
- Dr D M Simpson, Clinical Neurophysiology Laboratories and Neuro-AIDS Program, The Mount Sinai Medical Center, Box 1052, New York, NY 10029, USA; david.simpson{at}mssm.edu
- Received 31 July 2008
- Revised 30 September 2008
- Accepted 6 October 2008
- Published Online First 31 October 2008
Abstract
Background: While spasticity is commonly treated with oral agents or botulinum neurotoxin (BoNT) injection, these treatments have not been systematically compared.
Methods: This study performed a randomised, double-blind, placebo-controlled trial to compare injection of BoNT-Type A into spastic upper limb muscles versus oral tizanidine (TZD), or placebo, in 60 subjects with upper-limb spasticity due to stroke or traumatic brain injury (TBI). Wrist flexors were systematically injected, while other upper limb muscles were injected as per investigator judgement. Participants were randomised into three groups: (1) intramuscular BoNT plus oral placebo; (2) oral TZD plus intramuscular placebo; (3) intramuscular placebo plus oral placebo. The primary outcome was the difference in change in wrist flexor modified Ashworth score (MAS) between groups. Other outcome measures included MAS at elbow and finger joints, Disability Assessment Scale (DAS) and adverse events (AE).
Results: BoNT produced greater tone reduction than TZD or placebo in finger and wrist flexors at week 3 (p<0.001 vs TZD; p<0.02 vs placebo) and 6 (p = 0.001 vs TZD; p = 0.08 vs placebo), and greater improvement in the cosmesis domain of the DAS at week 6 (p<0.01). TZD was not superior to placebo in tone reduction at either time point (p≥0.09). The incidence of AE related to study treatment was higher with TZD than in the BoNT (p<0.01) or placebo groups (p = 0.001).
Conclusions: BoNT is safer and more effective than TZD in reducing tone and disfigurement in upper-extremity spasticity, and may be considered as first-line therapy for this disorder.
Footnotes
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Competing interests: DMS and JMG received consultancy fees and research grants from Allergan, Solstice and Merz; SAY received consultancy fees from Allergan, Merz, and Athena Neurosciences and research grants from Athena, and Medtronic; RB received consulting fees, educational grants and speaking honoraria from Allergan and a research grant from Merz; AB received consultancy fees from Merz and research grants from Allergan, Ipsen and Merz, and provided expert testimony related to botulinum toxin.
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Funding: DMS of Mount Sinai School of Medicine is the sponsor of the study. The study was funded by an unrestricted grant by Allergan, Inc. Allergan had no influence on the design, interpretation or reporting of the study.
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Clinical trial registration: This study is registered at http://clinicaltrials.gov/:NCT00430196.
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Ethics approval: Ethics approval was provided by the following Institutional Review Boards: Mount Sinai Medical Center, New York, NY University of Rochester, Rochester, NY Indiana University School of Medicine, Indianapolis, IN Burke Rehabilitation Hospital, White Plains, NY Neurology Group of Bergen County, Ridgewood, NJ Long Island Jewish Medical Center, New Hyde Park, NY Methodist Rehabilitation Center, Jackson, MS North Staffordshire Rehabilitation Centre, University Hospital of North Staffordshire, Stoke on Trent, UK University of Kentucky Medical Center, Lexington KY.
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Patient consent: Obtained.
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See Editorial Commentary, p 359
