Pharmacokinetics and pharmacodynamics of incobotulinumtoxinA influencing the clinical efficacy in post-stroke spasticity

ABSTRACT

Introduction: Post-stroke spasticity is a disabling neurological condition and may have a significant impact on quality of life. Ability to carry out activities of daily living is often compromised and painful contractures in the affected limbs may also develop. The prevalence of spasticity may be as high as 40% within the first year after the initial stroke event. Management of this condition focuses on improving muscle tone, function and pain. IncobotulinumtoxinA is effective in treating focal spasticity.

Areas covered: This review will summarize outcomes from incobotulinumtoxin A phase III trials in upper limb spasticity. Pharmacodynamics and pharmacokinetics will also be discussed along with future studies and possible indications. Literature searches used for this review include; PubMed and www.clinicaltrials.gov searches. Congress abstracts and case reports are not included.

Expert opinion: IncobotulinumtoxinA, is a 150 kiloDalton neurotoxin without complexing proteins and is well tolerated in patients with spasticity. There is an 80% improvement reported on spasticity and disability in several phase III studies. In the future, higher doses for upper and lower limb spasticity may be considered. Antibody formation does not seem to limit the administration of higher doses. Prospective studies are evaluating the efficacy of incobotulinumtoxin in children and adolescents with cerebral palsy. Furthermore, the clinical efficacy and immunogenic status of other botulinum neurotoxin A subtypes are currently under investigation.

KEYWORDS:

• incobotulinumtoxinA
• botulinum toxin A
• Xeomin
• spasticity
• post-stroke spasticity
• pharmacology
• pharmacodynamics
• treatment efficacy

Acknowledgement

The authors would like to thank Dr Fiona M Molloy, consultant neurologist and

Neurophysiologist, Clinical Director of the Clinical Neurophysiology Department,

Beaumont Hospital, Dublin, Ireland, for editing and her valuable comments on the manuscript.

Declaration of Interest

KE Zeuner has received lecture fees from Allergan, Ipsen, Merz; research support from The German Research Foundation, University of Kiel, Benign Essential Bleparospasm Foundation, Allergan and Ipsen. G Deuschl has received lecture fees from Orion, Lundbeck, Teva, Pfizer; G Deuschl has served as a consultant for TEVA, Medtronic, Novartis; G Deuschl has received royalties from Thieme Publishers Funding, The German Research Council, German Ministry of Education and Health, and Medtronic. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.