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Drugs

, Volume 76, Issue 14, pp 1373–1379 | Cite as

IncobotulinumtoxinA: A Review in Upper Limb Spasticity

  • Yvette N. LambEmail author
  • Lesley J. Scott
Adis Drug Evaluation

Abstract

Intramuscular incobotulinumtoxinA (Xeomin®) is indicated for the treatment or improvement of adult patients with upper limb spasticity (featured indication), cervical dystonia, blepharospasm and glabellar lines. It is a highly purified formulation of botulinum toxin type A that inhibits acetylcholine signalling at neuromuscular junctions, reducing muscle hypertonia. This narrative review discusses the clinical use of incobotulinumtoxinA in adults with upper limb spasticity and summarizes its pharmacological properties. In single-treatment phase 3 trials, compared with placebo, incobotulinumtoxinA treatment improved muscle tone, global spasticity, functional spasticity-related disability and some aspects of carer burden in adults with upper limb spasticity. These beneficial effects of incobotulinumtoxinA on muscle tone were generally maintained in extension studies, in which up to five additional incobotulinumtoxinA treatments were administered. Functional spasticity-related disability and carer burden were also reduced during longer-term incobotulinumtoxinA treatment. IncobotulinumtoxinA was generally well tolerated in clinical trials, with relatively few patients experiencing treatment-related adverse events, most of which were of mild to moderate intensity. No neutralizing antibodies that would potentially cause secondary nonresponse against incobotulinumtoxinA were detected after single and multiple treatments in these trials or in phase 3 and 4 trials of incobotulinumtoxinA in other indications, which may be an advantage of this purified formulation. Further research would help to more fully determine the impact of neurotoxin purification in terms of reducing the potential risk of immunogenic responses during long-term treatment. Hence, incobotulinumtoxinA is a useful treatment option for upper limb spasticity in adult patients.

Keywords

Target Domain Elbow Flexor Cervical Dystonia onabotulinumtoxinA Wrist Flexor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

During the peer review process, the manufacturer of incobotulinumtoxinA was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with Ethical Standards

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Yvette Lamb and Lesley Scott are salaried employees of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.

References

  1. 1.
    Lance JW. What is spasticity? Lancet. 1990;335(8689):606.CrossRefPubMedGoogle Scholar
  2. 2.
    Simpson DM. Clinical trials of botulinum toxin in the treatment of spasticity. Muscle Nerve. 1997;20(Suppl 6):169–75.CrossRefGoogle Scholar
  3. 3.
    Esquenazi A. Improvements in healthcare and cost benefits associated with botulinum toxin treatment of spasticity and muscle overactivity. Eur J Neurol. 2006;13(Suppl 4):27–34.CrossRefPubMedGoogle Scholar
  4. 4.
    Sommerfeld DK, Gripenstedt U, Welmer A-K. Spasticity after stroke: an overview of prevalence, test instruments, and treatments. Am J Phys Med Rehabil. 2012;91(9):814–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Bhakta BB. Management of spasticity in stroke. Br Med Bull. 2000;56(2):476–85.CrossRefPubMedGoogle Scholar
  6. 6.
    Santamato A. Safety and efficacy of incobotulinumtoxinA as a potential treatment for poststroke spasticity. Neuropsychiatr Dis Treat. 2016;12:251–63.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Abbruzzese G. The medical management of spasticity. Eur J Neurol. 2002;9(Suppl 1):30–4.CrossRefPubMedGoogle Scholar
  8. 8.
    Frevert J. Content of botulinum neurotoxin in Botox®/Vistabel®, Dysport®/Azzalure®, and Xeomin®/Bocouture®. Drugs R D. 2010;10(2):67–73.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Göschel H, Wohlfarth K, Frevert J, et al. Botulinum A toxin therapy: neutralizing and nonneutralizing antibodies—therapeutic consequences. Exp Neurol. 1997;147(1):96–102.CrossRefPubMedGoogle Scholar
  10. 10.
    Wenzel RG. Pharmacology of botulinum neurotoxin serotype A. Am J Health Syst Pharm. 2004;61(22 Suppl 6):S5–10.PubMedGoogle Scholar
  11. 11.
    Jost WH, Benecke R, Hauschke D, et al. Clinical and pharmacological properties of incobotulinumtoxinA and its use in neurological disorders. Drug Des Devel Ther. 2015;9:1913–26.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Blümel J, Frevert J, Schwaier A. Comparative antigenicity of three preparations of botulinum neurotoxin type A in the rabbit. Neurotox Res. 2006;9(2–3):238.Google Scholar
  13. 13.
    Jost WH, Blümel J, Grafe S. Botulinum neurotoxin type A free of complexing proteins (Xeomin®) in focal dystonia. Drugs. 2007;67(5):669–83.CrossRefPubMedGoogle Scholar
  14. 14.
    Merz Pharmaceuticals LLC. Xeomin (incobotulinumtoxinA) for injection, for intramuscular use: US prescribing information. 2015. http://www.xeomin.com/. Accessed 11 Aug 2016.
  15. 15.
    Merz Pharma UK Ltd. Xeomin 100 units: summary of product characteristics. 2014. http://www.medicines.org.uk/. Accessed 11 Aug 2016.
  16. 16.
    Dolly JO, Aoki KR. The structure and mode of action of different botulinum toxins. Eur J Neurol. 2006;13(Suppl 4):1–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Elovic EP, Munin MC, Kaňovský P, et al. Randomized, placebo-controlled trial of incobotulinumtoxina for upper-limb post-stroke spasticity. Muscle Nerve. 2016;53(3):415–21.CrossRefPubMedGoogle Scholar
  18. 18.
    Kaňovský P, Slawek J, Denes Z, et al. Efficacy and safety of botulinum neurotoxin NT 201 in poststroke upper limb spasticity. Clin Neuropharmacol. 2009;32(5):259–65.CrossRefPubMedGoogle Scholar
  19. 19.
    Elovic E, Munin MC, Kaňovský P, et al. Efficacy and safety of repeated incobotulinumtoxinA injections for upper-limb post-stroke spasticity [abstract]. In: Annual Assembly of the AAPM&R. 2015.Google Scholar
  20. 20.
    Kaňovský P, Slawek J, Denes Z, et al. Efficacy and safety of treatment with incobotulinum toxin A (botulinum neurotoxin type A free from complexing proteins; NT 201) in post-stroke upper limb spasticity. J Rehabil Med. 2011;43(6):486–92.CrossRefPubMedGoogle Scholar
  21. 21.
    Barnes M, Schnitzler A, Medeiros L, et al. Efficacy and safety of NT 201 for upper limb spasticity of various etiologies: a randomized parallel-group study. Acta Neurol Scand. 2010;122(4):295–302.CrossRefPubMedGoogle Scholar
  22. 22.
    Fiore P, Santamato A, Ranieri M, et al. Treatment of upper limb spasticity after stroke: one-year safety and efficacy of botulinum toxin type A NT201. Int J Immunopathol Pharmacol. 2012;25(Suppl 1):57S–62S.PubMedGoogle Scholar
  23. 23.
    Simpson DM, Hallett M, Ashman EJ, et al. Practice guideline update summary: botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache. Neurology. 2016;86:1–9.CrossRefGoogle Scholar
  24. 24.
    Teasell R, Foley N, Pereira S, et al. Evidence to practice: botulinum toxin in the treatment of spasticity post stroke. Top Stroke Rehabil. 2012;19(2):115–21.CrossRefPubMedGoogle Scholar
  25. 25.
    Naumann M, Boo LM, Ackerman AH, et al. Immunogenicity of botulinum toxins. J Neural Transm. 2013;120:275–90.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

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