Vol 55, No 2 (2021)
Research Paper
Published online: 2021-01-12

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Spasticity in practice (SPACE): an international non-interventional study of botulinum neurotoxin type A in treatment-naïve subjects with spasticity

Julian Harriss1, Nicolas Roche2, Carlos Cantú-Brito3, Svetlana Khatkova4, Patrik Säterö5, Susanne Heitmann6, Olivier Simon7, Christine Kliebe-Frisch8, Georg Comes9, Wolfgang H. Jost1011
Pubmed: 33433902
Neurol Neurochir Pol 2021;55(2):165-173.


Aim of the study. SPACE, a prospective, non-interventional, open-label, multinational study, investigated physicians’ and subjects’ assessment of safety, efficacy, and health-related quality of life (HRQoL) following botulinum neurotoxin type A (BoNT-A) treatment to understand real-world clinical usage for the management of focal and multifocal spasticity.

Clinical rationale for the study. Treatment guidelines recommend the use of BoNT-A for the management of spasticity in adults. This study assessed how physicians use BoNT-A therapy in real-world clinical practice, and provided evidence on long-term safety and efficacy over a period of up to 2 years.

Materials and methods. BoNT treatment-naïve adults with spasticity of any aetiology received any BoNT-A formulation at their physician’s discretion, and were observed for ≤ 8 treatment cycles (≤ 2 years). Daily practice information, physician’s global assessments of tolerability and efficacy, and HRQoL were documented. Incidences of adverse drug reactions or all adverse events were documented for non-Mexican subjects and for Mexican subjects, respectively, due to protocol differences based on local regulatory requirements.

Results. A total of 701 subjects were enrolled (safety population; nine countries). Physicians rated the tolerability of BoNT-A as ‘very good’ or ‘good’ for 88.2–97.4% of subjects throughout the study (subject numbers declined throughout this non-interventional study). Adverse drug reactions were reported for 16/600 (2.7%) of the non-Mexican subjects, with two considered to be ‘definitely related’ to treatment (injection-site haematoma, n = 1; botulism, n = 1). For 687 subjects, efficacy was rated ‘very good’ or ‘good’ by most physicians and subjects. Improvements in HRQoL were observed.

Conclusions and clinical implications. Throughout this 2-year study, BoNT-A treatment was generally well-tolerated, effective, and associated with an improved HRQoL. This study makes a valuable contribution to the broader understanding of how physicians use BoNT-A therapy to manage spasticity in real-world clinical practice.

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  1. 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.
  2. Royal College of Physicians, British Society of Rehabilitation Medicine, Chartered Society of Physiotherapy, Spasticity in adults: management using botulinum toxin. National guidelines 2018 https://www rcplondon ac uk/sites/default/files/documents/spasticity-in-adults-management-botulinum-toxin pdf Accessed. ; 2: October.
  3. 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): 1818–1826.
  4. 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.
  5. Merz Pharmaceuticals LLC. Highlights of Prescribing Information – Xeomin®. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125360s074lbl.pdf. Accessed May. ; 17: 2019.
  6. Merz Pharma UK Ltd. XEOMIN® (50/100/200) Summary of Product Characteristics. 2020. https://www.medicines.org.uk/emc/product/2162/smpc. Accessed March. ; 19: 2020.
  7. Allergan Inc. Highlights of Prescribing Information - Botox®. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/103000s5309lbl.pdf. Accessed June. ; 3: 2019.
  8. Allergan Ltd. Botox® 100 U Summary of Product Characteristics. 2020. https://www.medicines.org.uk/EMC/medicine/112/SPC/ (March 19, 2020).
  9. Ipsen Biopharm Ltd. Highlights of Prescribing Information - Dysport®. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125274s115lbl.pdf. Accessed October. ; 16: 2019.
  10. Ipsen Biopharm Ltd. Dysport® 500 U Summary of Product Characteristics. 2020. https://www.medicines.org.uk/emc/medicine/32114. (19, 2020).
  11. Bakheit AMO, Fedorova NV, Skoromets AA, et al. The beneficial antispasticity effect of botulinum toxin type A is maintained after repeated treatment cycles. J Neurol Neurosurg Psychiatry. 2004; 75(11): 1558–1561.
  12. Gordon MF, Brashear A, Elovic E, et al. BOTOX Poststroke Spasticity Study Group. Repeated dosing of botulinum toxin type A for upper limb spasticity following stroke. Neurology. 2004; 63(10): 1971–1973.
  13. Elovic EP, Brashear A, Kaelin D, et al. Repeated treatments with botulinum toxin type a produce sustained decreases in the limitations associated with focal upper-limb poststroke spasticity for caregivers and patients. Arch Phys Med Rehabil. 2008; 89(5): 799–806.
  14. Kanovský 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): 259–265.
  15. Kaji R, Osako Y, Suyama K, et al. GSK1358820 Spasticity Study Group. Botulinum toxin type A in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial. J Neurol. 2010; 257(8): 1330–1337.
  16. 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): 486–492.
  17. 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. The Lancet Neurology. 2015; 14(10): 992–1001.
  18. 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): 415–421.
  19. 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.
  20. Wissel J, Bensmail D, Ferreira JJ, et al. TOWER study investigators. Safety and efficacy of incobotulinumtoxinA doses up to 800 U in limb spasticity: The TOWER study. Neurology. 2017; 88(14): 1321–1328.
  21. Bakheit AM, Zakine B, Maisonobe P, et al. The profile of patients and current practice of treatment of upper limb muscle spasticity with botulinum toxin type A: an international survey. Int J Rehabil Res. 2010; 33(3): 199–204.
  22. Mohammadi B, Balouch SA, Dengler R, et al. Long-term treatment of spasticity with botulinum toxin type A: an analysis of 1221 treatments in 137 patients. Neurol Res. 2010; 32(3): 309–313.
  23. Sarzyńska-Długosz I, Szczepańska-Szerej A, Drużdż A, et al. Real-world effectiveness of abobotulinumtoxinA (Dysport®) in adults with upper limb spasticity in routine clinical practice: an observational study. Neurol Neurochir Pol. 2020; 54(1): 90–99.
  24. 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).
  25. Carr-Hill RA. EuroQol Group. EuroQol--a new facility for the measurement of health-related quality of life. Health Policy. 1990; 16(3): 199–208.
  26. Dressler D, Bigalke H. Pharmacology of botulinum toxin drugs. Manual of Botulinum Toxin Therapy. : 13–22.
  27. Bensmail D, Hanschmann A, Wissel J. Satisfaction with botulinum toxin treatment in post-stroke spasticity: results from two cross-sectional surveys (patients and physicians). J Med Econ. 2014; 17(9): 618–625.
  28. Santamato A, Micello MF, Panza F, et al. Can botulinum toxin type A injection technique influence the clinical outcome of patients with post-stroke upper limb spasticity? A randomized controlled trial comparing manual needle placement and ultrasound-guided injection techniques. J Neurol Sci. 2014; 347(1-2): 39–43.
  29. Ward A, Wissel J, Borg J, et al. Functional goal achievement in post-stroke spasticity patients: The BOTOX® Economic Spasticity Trial (BEST). Journal of Rehabilitation Medicine. 2014; 46(6): 504–513.
  30. Ware J, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996; 34(3): 220–233.

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