Efficacy of incobotulinumtoxinA for Spasticity-Associated Pain in a Series of Patients with Spasticity of Diverse Etiologies

Main Article Content

Alexandre Camoes-Barbosa

Abstract

Background: Spasticity is a motor disorder that appears as a cause of upper and lower limb motor disability, frequently causing pain. IncobotulinumtoxinA (IncoA) has proved effective for treating diverse musculoskeletal pathologies, including spasticity and spasticity-related pain.


Aims: The aim was to determine the efficacy of IncoA for the treatment of pain associated to limb spasticity of diverse etiologies.


Methods: Prospective, single-center study including 30 patients treated with IncoA between May and August 2021 at the University Hospital Center of Central Lisbon (Lisbon, Portugal). Primary endpoint was improvement in spasticity-related pain, assessed by employing pain numerical rating scale for pain at baseline and 12 weeks post-injection, scoring between 0 (no pain) and 10 (severe pain).


Results: Patients showed spasticity due to different etiologies, mainly ischemic stroke (46.7%), hemorrhagic stroke (23.3%) and cerebral palsy (20.0%). Mean pain score significantly decreased from baseline (mean: 6.8, range: 2-10) to 12 weeks post-injection (mean: 1.6; range: 0-5). Mean reduction of pain was of -5.2 points (95%CI: -5.9, -4.5). All patients achieved minimum clinically significant difference in pain reduction, showing sustained effect over 12 weeks regardless of spasticity etiology.


Conclusion: IncoA may be considered as an alternative for the treatment of spasticity-associated pain of diverse etiologies in upper and lower limbs.

Keywords: spasticity, pain, incobotulinumtoxinA, efficacy

Article Details

How to Cite
CAMOES-BARBOSA, Alexandre. Efficacy of incobotulinumtoxinA for Spasticity-Associated Pain in a Series of Patients with Spasticity of Diverse Etiologies. Medical Research Archives, [S.l.], v. 11, n. 5, may 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3590>. Date accessed: 03 oct. 2024. doi: https://doi.org/10.18103/mra.v11i5.3590.
Section
Research Articles

References

1. Lance J. W. Symposium synopsis. In: Feldman R. G., Young R. R., Koella W. P., editors. Spasticity: disordered motor control. 1980. pp. 485–494.
2. Trompetto C, Marinelli L, Mori L, et al. Pathophysiology of spasticity: implications for neurorehabilitation. Biomed Res Int. 2014;2014:354906.
doi: 10.1155/2014/354906.
3. Olsson MC, Krüger M, Meyer LH, et al. Fibre type-specific increase in passive muscle tension in spinal cord-injured subjects with spasticity. J Physiol. 2006;577(Pt 1):339-52. doi: 10.1113/jphysiol.2006.116749.
4. Smith LR, Lee KS, Ward SR, et al. Hamstring contractures in children with spastic cerebral palsy result from a stiffer extracellular matrix and increased in vivo sarcomere length. J Physiol. 2011;589(Pt 10):2625-39.
doi: 10.1113/jphysiol.2010.203364.
5. American Association of Neurological Surgeons. Spasticity, https://www.aans.org/Patients/NeurosurgicalConditions-and-Treatments/Spasticity, (accessed 23 September 2021).
6. Smania N, Picelli A, Munari D, et al. Rehabilitation procedures in the management of spasticity. Eur J Phys Rehabil Med. 2010;46(3):423-38.
7. Vuagnat H, Chantraine A. Shoulder pain in hemiplegia revisited: contribution of functional electrical stimulation and other therapies. J Rehabil Med. 2003;35(2):49-54. doi: 10.1080/16501970306111.
8. Wissel J, Schelosky LD, Scott J, et al. Early development of spasticity following stroke: a prospective, observational trial. J Neurol. 2010;257(7):1067-72. doi: 10.1007/s00415-010-5463-1.
9. Zorowitz RD, Gillard PJ, Brainin M. Poststroke spasticity: sequelae and burden on stroke survivors and caregivers. Neurology. 2013;80(3 Suppl 2):S45-52. doi: 10.1212/WNL.0b013e3182764c86.
10. Doan QV, Brashear A, Gillard PJ, et al. Relationship between disability and health-related quality of life and caregiver burden in patients with upper limb poststroke spasticity. PM R. 2012;4(1):4-10. doi: 10.1016/j.pmrj.2011.10.001.
11. Shaikh A, Phadke CP, Ismail F, et al. Relationship between botulinum toxin, spasticity, and pain: a survey of patient perception. Can J Neurol Sci. 2016;43(2):311-5. doi: 10.1017/cjn.2015.321.
12. Wissel J, Ganapathy V, Ward AB, et al. OnabotulinumtoxinA improves pain in patients with post-stroke spasticity: findings from a randomized, double-blind, placebo-controlled trial. J Pain Symptom Manage. 2016;52(1):17-26. doi: 10.1016/j.jpainsymman.2016.01.007.
13. Wissel J, Camões-Barbosa A, Comes G, et al. Pain Reduction in Adults with Limb Spasticity Following Treatment with IncobotulinumtoxinA: A Pooled Analysis. Toxins (Basel). 2021;13(12):887. doi: 10.3390/toxins13120887.
14. Mckinnon CT, Meehan EM, Harvey AR, et al. Prevalence and characteristics of pain in children and young adults with cerebral palsy: a systematic review. Dev Med Child Neurol. 2019;61(3):305-314.
doi: 10.1111/dmcn.14111.
15. Lejeune T, Khatkova S, Turner-Stokes L, et al. Abobotulinumtoxina injections in shoulder muscles to improve adult upper limb spasticity: results from a phase 4 real-world study and a phase 3 open-label trial. J Rehabil Med. 2020;52(6):jrm00068.
doi: 10.2340/16501977-2695.
16. Wissel J, Müller J, Dressnandt J, et al. Management of spasticity associated pain with botulinum toxin A. J Pain Symptom Manage. 2000;20(1):44-9. doi: 10.1016/s0885-3924(00)00146-9.
17. Ward AB, Kadies M. The management of pain in spasticity. Disabil Rehabil. 2002;24(8):443-53. doi: 10.1080/09638280110108878.
18. Chang E, Ghosh N, Yanni D, et al. A review of spasticity treatments: pharmacological and interventional approaches. Crit Rev Phys Rehabil Med. 2013;25(1-2):11-22. doi: 10.1615/CritRevPhysRehabilMed.2013007945.
19. Fitterer JW, Picelli A, Winston P. A novel approach to new-onset hemiplegic shoulder pain with decreased range of motion using targeted diagnostic nerve blocks: the ViVe algorithm. Front Neurol. 2021;12:668370. doi: 10.3389/fneur.2021.668370.
20. Wissel J, Ward AB, Erztgaard P, et al. European consensus table on the use of botulinum toxin type A in adult spasticity. J Rehabil Med. 2009;41(1):13-25. doi: 10.2340/16501977-0303.
21. Esquenazi A, Novak I, Sheean G, et al. International consensus statement for the use of botulinum toxin treatment in adults and children with neurological impairments--introduction. Eur J Neurol. 2010;17 Suppl 2:1-8. doi: 10.1111/j.1468-1331.2010.03125.x.
22. 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: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016;86(19):1818-26. doi: 10.1212/WNL.0000000000002560.
23. Royal College of Physicians, British Society of Rehabilitation Medicine, Chartered Society of Physiotherapy, Association of Chartered Physiotherapists in Neurology, Royal College of Occupational Therapists. Spasticity in adults: management using botulinum toxin. National guidelines, https://www.rcplondon.ac.uk/guidelines-policy/spasticity-adults-management-using-botulinum-toxin (2018, accessed 23 September 2021)
24. Sunnerhagen KS, Goldstein LB, Cramer SC, et al. Poststroke chronic disease management: towards improved identification and interventions for poststroke spasticity related complications. Int J Stroke. 2011;6:42-46. doi: 10.1111/j.1747-4949.2010.00539.x.
25. Bartolo M, Chiò A, Ferrari S, et al. Assessing and treating pain in movement disorders, amyotrophic lateral sclerosis, severe acquired brain injury, disorders of consciousness, dementia, oncology and neuroinfectivology. Evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation. Eur J Phys Rehabil Med. 2016;52(6):841-854.
26. Turner-Stokes L, Fheodoroff K, Jacinto J, et al. Results from the Upper Limb International Spasticity Study-II (ULISII): a large, international, prospective cohort study investigating practice and goal attainment following treatment with botulinum toxin A in real-life clinical management. BMJ Open. 2013;3(6):e002771. doi: 10.1136/bmjopen-2013-002771.
27. Turner-Stokes L, Jacinto J, Fheodoroff K, et al. Assessing the effectiveness of upper-limb spasticity management using a structured approach to goal-setting and outcome measurement: first cycle results from the ULIS-III Study. J Rehabil Med. 2021;53(1):jrm00133. doi: 10.2340/16501977-2770.
28. Slawek J, Bogucki A, Reclawowicz D. Botulinum toxin type A for upper limb spasticity following stroke: an open-label study with individualised, flexible injection regimens. Neurol Sci. 2005;26(1):32-9. doi: 10.1007/s10072-005-0379-8.
29. 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. doi: 10.1111/j.1600-0404.2010.01354.x.
30. 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. doi: 10.1002/mus.24776.
31. Wissel J, Bensmail D, Ferreira JJ, et al. Safety and efficacy of incobotulinumtoxinA doses up to 800 U in limb spasticity: the TOWER study. Neurology. 2017;88(14):1321-1328. doi: 10.1212/WNL.0000000000003789.
32. Fheodoroff K, Rekand T, Medeiros L, et al. Quality of life in subjects with upper- and lower-limb spasticity treated with incobotulinumtoxinA. Health Qual Life Outcomes. 2020;18(1):51. doi: 10.1186/s12955-020-01304-4.
33. Dunne JW, Gracies JM, Hayes M, et al. Multicentre Study Group. A prospective, multicentre, randomized, double-blind, placebo-controlled trial of onabotulinumtoxinA to treat plantarflexor/invertor overactivity after stroke. Clin Rehabil. 2012;26(9):787-97. doi: 10.1177/0269215511432016.
34. Rousseaux M, Daveluy W, Kozlowski O, et al. Onabotulinumtoxin-A injection for disabling lower limb flexion in hemiplegic patients. NeuroRehabilitation. 2014;35(1):25-30. doi: 10.3233/NRE-141093.
35. Gracies JM, Brashear A, Jech R, et al. Safety and efficacy of abobotulinumtoxinA for hemiparesis in adults with upper limb spasticity after stroke or traumatic brain injury: a double-blind randomised controlled trial. Lancet Neurol. 2015;14(10):992-1001. doi: 10.1016/S1474-4422(15)00216-1.
36. Fujimura K, Kagaya H, Onaka H, et al. Improvement in disability assessment scale after botulinum toxin A treatment for upper limb spasticity. Jpn J Compr Rehabil Sci. 2017;8:4-9. doi: 10.1159/000499907.
37. Rosales RL, Balcaitiene J, Berard H, et al. Early AbobotulinumtoxinA (Dysport®) in post-stroke adult upper limb spasticity: ONTIME pilot study. Toxins (Basel). 2018;10(7):253. doi: 10.3390/toxins10070253.
38. Wein T, Esquenazi A, Jost WH, et al. OnabotulinumtoxinA for the treatment of poststroke distal lower limb spasticity: a randomized trial. PM R. 2018;10(7):693-703.
39. Masakado Y, Abo M, Kondo K, et al. Efficacy and safety of incobotulinumtoxinA in post-stroke upper-limb spasticity in Japanese subjects: results from a randomized, double-blind, placebo-controlled study (J-PURE). J Neurol. 2020;267(7):2029-2041. doi: 10.1016/j.pmrj.2017.12.006.
40. Wissel J, Bensmail D, Scheschonka A, et al. Post hoc analysis of the improvement in shoulder spasticity and safety observed following treatment with incobotulinumtoxinA. J Rehabil Med. 2020;52(3):jrm00028. doi: 10.2340/16501977-2651.
41. Pirazzini M, Rossetto O, Eleopra R, et al. Botulinum neurotoxins: biology, pharmacology, and toxicology. Pharmacol Rev. 2017;69(2):200-235. doi: 10.1124/pr.116.012658.
42. Baker JA, Pereira G. The efficacy of Botulinum Toxin A for spasticity and pain in adults: a systematic review and meta-analysis using the grades of recommendation, assessment, development and evaluation approach. Clin Rehabil. 2013;27:1084-1096. doi: 10.1177/0269215513491274.
43. Brown EA, Schütz SG, Simpson DM. Botulinum toxin for neuropathic pain and spasticity: an overview. Pain Manag. 2014;4(2):129-151. doi: 10.2217/pmt.13.75.
44. Li X, Coffield JA. Structural and functional interactions between transient receptor potential vanilloid subfamily 1 and botulinum neurotoxin serotype A. PLoS One. 2016;11(1):e0143024. doi: 10.1371/journal.pone.0143024.
45. Karcioglu O, Topacoglu H, Dikme O, et al. A systematic review of the pain scales in adults: Which to use? Am J Emerg Med. 2018;36(4):707-714. doi: 10.1016/j.ajem.2018.01.008.
46. Kendrick DB, Strout TD. The minimum clinically significant difference in patient-assigned numeric scores for pain. Am J Emerg Med. 2005;23(7):828-32. doi: 10.1016/j.ajem.2005.07.009.
47. Esquenazi A, Novak I, Sheean G, et al. International consensus statement for the use of botulinum toxin treatment in adults and children with neurological impairments-introduction. Eur J Neurol 2010; 17 (Suppl. 2): 1–8. doi: 10.1111/j.1468-1331.2010.03125.x.
48. 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: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2016; 86: 1818–1826 doi: 10.1212/WNL.0000000000002560.
49. Cosgrove AP, Graham HK. Botulinum Toxin A in the management of spasticity with cerebral palsy. Br J Surg. 1992;74B:135-136. doi: 10.1111/j.1469-8749.1994.tb11864.x.
50. Lamb YN, Scott LJ. IncobotulinumtoxinA: a review in upper limb spasticity. Drugs. 2016;76(14):1373-1379. doi: 10.1007/s40265-016-0630-z.
51. Papadonikolakis A, Vekris M, Korompilias A, et al. Botulinum A toxin for treatment of lower limb spasticity in cerebral palsy gait analysis in 49 patients. Acta Orthop Scand. 2003;74(6):749-755. doi: 10.1080/00016470310018315.
52. Moccia M, Frau J, Carotenuto A, et al. Botulinum toxin for the management of spasticity in multiple sclerosis: the Italian botulinum toxin network study. Neurol Sci. 2020;41(10):2781-2792. doi: 10.1007/s10072-020-04392-8.
53. Jacobson D, Löwing K, Kullander K, et al. A first clinical trial on botulinum toxin-A for chronic muscle-related pain in cerebral palsy. Front Neurol. 2021;12:696218. doi: 10.3389/fneur.2021.696218.
54. Pedreira G, Cardoso E, Melo A. Botulinum toxin type A for refractory post-stroke shoulder pain. Arq. Neuropsiquiatr. 2008;66(2A):213-215. doi: 10.1590/s0004-282x2008000200014.
55. Santamato A, Panza F, Ranieri M, et al. Efficacy and safety of higher doses of botulinum toxin type A NT 201 free from complexing proteins in the upper and lower limb spasticity after stroke. J Neural Transm (Vienna). 2013;120(3):469-76. doi: 10.1007/s00702-012-0892-x.56. Intiso D, Simone V, Di Rienzo F, et al. High doses of a new botulinum toxin type A (NT-201) in adult patients with severe spasticity following brain injury and cerebral palsy. NeuroRehabilitation. 2014;34(3):515-22. doi: 10.3233/NRE-141052.
56. Dunne JW, Heye N, Dunne SL. Treatment of chronic limb spasticity with botulinum toxin A. J Neurol Neurosurg Psychiatry. 1995;58(2):232-235. doi: 10.1136/jnnp.58.2.232.
57. Touma J, May T, Isaacson AC. Cervical myofascial pain. [Updated 2020 Jul 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507825/
58. Brashear A, Gordon MF, Elovic E, et al. Intramuscular injection of botulinum toxin for the treatment of wrist and finger spasticity after a stroke. N Engl J Med. 2002;347(6):395-400. doi: 10.1056/NEJMoa011892.
59. Heinen F, Kanovsk P, Schroeder AS, et al. IncobotulinumtoxinA for the treatment of lower-limb spasticity in children and adolescents with cerebral palsy: a phase 3 study. J Pediatr Rehabil Med. 2021;14(2):183-97. doi: 10.3233/PRM-210040
60. Kanovsk P, Heinen F, Schroeder AS, et al. Safety and efficacy of repeat long-term incobotulinumtoxinA treatment for lower limb or combined upper/lower limb spasticity in children with cerebral palsy. J Pediatr Rehabil Med. 2022;15(1):113-27. doi: 10.3233/PRM-210041
61. Dabrowski E, Chambers HG, Gaebler-Spira D, et al. IncobotulinumtoxinA ´ efficacy/safety in upper-limb spasticity in pediatric cerebral palsy: Randomized controlled trial. Pediatr Neurol. 2021;123:10-20. doi: 10.1016/j.pediatrneurol.2021.05.014
62. Bonfert M, Heinen F, Kaňovský P, et al. Spasticity-related pain in children/adolescents with cerebral palsy. Part 2 IncobotulinumtoxinA efficacy results from a pooled analysis. J Pediatr Rehabil Med. 2022. doi: 10.3233/PRM-220020.