Vol 55, No 2 (2021)
Review Article
Published online: 2021-04-02

open access

Page views 1617
Article views/downloads 1659
Get Citation

Connect on Social Media

Connect on Social Media

Botulinum toxin type-A preparations are not the same medications — clinical studies (Part 2)

Jarosław Sławek1, Andrzej Bogucki2, Marcin Bonikowski3, Halina Car4, Malgorzata Dec-Ćwiek5, Artur Drużdż6, Dariusz Koziorowski7, Iwona Sarzyńska-Długosz8, Monika Rudzińska9
Pubmed: 33797748
Neurol Neurochir Pol 2021;55(2):141-157.

Abstract

The growing number of Botulinum neurotoxin type A (BoNT/A) preparations on the market has resulted in a search for pharmacological, clinical and pharmacoeconomic differences. Patients are occasionally switched from one botulinum toxin formulation to another.

The aim of this paper was to review studies that have made direct comparisons of the three major BoNT/A preparations presently on the market: ona-, abo- and incobotulinumtoxinA. We also review the single medication Class I pivotal and occasionally Class II-IV studies, as well as recommendations and guidelines to show how effective doses have been adopted in well-established indications such as blepharospasm, hemifacial spasm, cervical dystonia and adult spasticity.

Neither direct head-to-head studies nor single medication studies between all preparations allow the formation of universal conversion ratios. All preparations should be treated as distinct medications with respect to their summary of product characteristics when used in everyday practice.

Article available in PDF format

View PDF Download PDF file

References

  1. Sławek J, Car H, Bonikowski M, et al. Are botulinum toxin type A preparations really the same medication? A comparison of three botulinum toxin A for variations in labelled neurological indications. Neurol Neurochir Pol. 2010; 44(1): 43–64.
  2. Ferrari A, Manca M, Tugnoli V, et al. Pharmacological differences and clinical implications of various botulinum toxin preparations: a critical appraisal. Funct Neurol. 2018; 33(1): 7–18.
  3. Car H, Bogucki A, et al. Botulinum toxin type-A preparations are not the same medications – basic science (Part 1) . Neurol Neurochir Pol . 2021; xxxxxxxxxxxxxxxx.
  4. Allergan, Ltd. BOTOX® 100 U. Summary of product characteristics [webpage on the Internet]. Surrey, UK: Datapharm Communications Ltd; 2013. http://www.medicines.org.uk/emc/medicine/112 (October 8, 2020).
  5. Dysport® (abobotulinumtoxinA) [prescribing information]. Boulogne-Billancourt: IpsenBiopharm Ltd; 2012. (October 8, 2020).
  6. XEOMIN (50/100/200) units powder for solution for injection –summary of product characteristics. https://www.medicines.ie/medicines/xeomin-50-100-200-units-powder-for-solution-for-injection-34858/spc#! (November 2019).
  7. Marion MH, Sheehy M, Sangla S, et al. Dose standardisation of botulinum toxin. J Neurol Neurosurg Psychiatry. 1995; 59(1): 102–103.
  8. Sampaio C, Ferreira JJ, Simões F, et al. DYSBOT: a single-blind, randomized parallel study to determine whether any differences can be detected in the efficacy and tolerability of two formulations of botulinum toxin type A--Dysport and Botox--assuming a ratio of 4:1. Mov Disord. 1997; 12(6): 1013–1018.
  9. Nüssgens Z, Roggenkämper P. Comparison of two botulinum-toxin preparations in the treatment of essential blepharospasm. Graefes Arch Clin Exp Ophthalmol. 1997; 235(4): 197–199.
  10. Bihari K. Safety, effectiveness, and duration of effect of BOTOX after switching from Dysport for blepharospasm, cervical dystonia, and hemifacial spasm dystonia, and hemifacial spasm. Curr Med Res Opin. 2005; 21(3): 433–438.
  11. Marchetti A, Magar R, Findley L, et al. Retrospective evaluation of the dose of Dysport and BOTOX in the management of cervical dystonia and blepharospasm: the REAL DOSE study. Mov Disord. 2005; 20(8): 937–944.
  12. Bentivoglio AR, Ialongo T, Bove F, et al. Retrospective evaluation of the dose equivalence of Botox(®) and Dysport (®) in the management of blepharospasm and hemifacial spasm: a novel paradigm for a never ending story. Neurol Sci. 2012; 33(2): 261–267.
  13. Dressler D. Routine use of Xeomin® in patients previously treated with Botox®: long term results. European Journal of Neurology. 2009; 16: 2–5.
  14. Roggenkämper P, Jost WH, Bihari K, et al. NT 201 Blepharospasm Study Team. Efficacy and safety of a new Botulinum Toxin Type A free of complexing proteins in the treatment of blepharospasm. J Neural Transm (Vienna). 2006; 113(3): 303–312.
  15. Saad J, Gourdeau A. A direct comparison of onabotulinumtoxina (Botox) and IncobotulinumtoxinA (Xeomin) in the treatment of benign essential blepharospasm: a split-face technique. J Neuroophthalmol. 2014; 34(3): 233–236.
  16. Wabbels B, Reichel G, Fulford-Smith A, et al. Double-blind, randomised, parallel group pilot study comparing two botulinum toxin type A products for the treatment of blepharospasm. J Neural Transm (Vienna). 2011; 118(2): 233–239.
  17. Chundury RV, Couch SM, Holds JB, et al. Comparison of preferences between onabotulinumtoxinA (Botox) and incobotulinumtoxinA (Xeomin) in the treatment of benign essential blepharospasm. Ophthalmic Plast Reconstr Surg. 2013; 29(3): 205–207.
  18. Juarez H, Salvador S, Hernandez L, et al. et al.. Cost benefit assessment of two forms of botulinum toxin type A in different pathologies. Ann Neurol. 2011; 70: S21.
  19. Grosset DG, Tyrrell EG, Grosset KA. Switch from abobotulinumtoxinA (Dysport®) to incobotulinumtoxinA (Xeomin®) botulinum toxin formulation: a review of 257 cases. J Rehabil Med. 2015; 47(2): 183–186.
  20. Kollewe K, Mohammadi B, Köhler S, et al. Blepharospasm: long-term treatment with either Botox®, Xeomin® or Dysport®. J Neural Transm (Vienna). 2015; 122(3): 427–431.
  21. Jankovic J, Orman J. Botulinum A toxin for cranial-cervical dystonia: a double-blind, placebo-controlled study. Neurology. 1987; 37(4): 616–623.
  22. Yoshimura DM, Aminoff MJ, Tami TA, et al. Treatment of hemifacial spasm with botulinum toxin. Muscle Nerve. 1992; 15(9): 1045–1049.
  23. Girlanda P, Quartarone A, Sinicropi S, et al. Unilateral injection of botulinum toxin in blepharospasm: single fiber electromyography and blink reflex study. Mov Disord. 1996; 11(1): 27–31.
  24. Truong D, Comella C, Fernandez HH, et al. Dysport Benign Essential Blepharospasm Study Group. Efficacy and safety of purified botulinum toxin type A (Dysport) for the treatment of benign essential blepharospasm: a randomized, placebo-controlled, phase II trial. Parkinsonism Relat Disord. 2008; 14(5): 407–414.
  25. Jankovic J, Comella C, Hanschmann A, et al. Efficacy and safety of incobotulinumtoxinA (NT 201, Xeomin) in the treatment of blepharospasm-a randomized trial. Mov Disord. 2011; 26(8): 1521–1528.
  26. Odergren T, Hjaltason H, Kaakkola S, et al. A double blind, randomised, parallel group study to investigate the dose equivalence of Dysport and Botox in the treatment of cervical dystonia. J Neurol Neurosurg Psychiatry. 1998; 64(1): 6–12.
  27. Ranoux D, Gury C, Fondarai J, et al. Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia. J Neurol Neurosurg Psychiatry. 2002; 72(4): 459–462.
  28. Rystedt A, Zetterberg L, Burman J, et al. A Comparison of Botox 100 U/mL and Dysport 100 U/mL Using Dose Conversion Ratio 1: 3 and 1: 1.7 in the Treatment of Cervical Dystonia: A Double-Blind, Randomized, Crossover Trial. Clin Neuropharmacol. 2015; 38(5): 170–176.
  29. Yun JiY, Kim JW, Kim HT, et al. Dysport and Botox at a ratio of 2.5:1 units in cervical dystonia: a double-blind, randomized study. Mov Disord. 2015; 30(2): 206–213.
  30. Benecke R, Jost WH, Kanovsky P, et al. A new botulinum toxin type A free of complexing proteins for treatment of cervical dystonia. Neurology. 2005; 64(11): 1949–1951.
  31. Lorentz IT, Subramaniam SS, Yiannikas C. Treatment of idiopathic spasmodic torticollis with botulinum toxin A: a double-blind study on twenty-three patients. Mov Disord. 1991; 6(2): 145–150.
  32. Moore AP, Blumhardt LD. A double blind trial of botulinum toxin "A" in torticollis, with one year follow up. J Neurol Neurosurg Psychiatry. 1991; 54(9): 813–816.
  33. Lu CS, Chen RS, Tsai CH. Double-blind, placebo-controlled study of botulinum toxin injections in the treatment of cervical dystonia. J Formos Med Assoc. 1995; 94(4): 189–192.
  34. Poewe W, Deuschl G, Nebe A, et al. What is the optimal dose of botulinum toxin A in the treatment of cervical dystonia? Results of a double blind, placebo controlled, dose ranging study using Dysport. German Dystonia Study Group. J Neurol Neurosurg Psychiatry. 1998; 64(1): 13–17.
  35. Truong D, Duane DD, Jankovic J, et al. Efficacy and safety of botulinum type A toxin (Dysport) in cervical dystonia: results of the first US randomized, double-blind, placebo-controlled study. Mov Disord. 2005; 20(7): 783–791.
  36. Comella CL, Jankovic J, Truong DD, et al. U.S. XEOMIN Cervical Dystonia Study Group. Efficacy and safety of incobotulinumtoxinA (NT 201, XEOMIN®, botulinum neurotoxin type A, without accessory proteins) in patients with cervical dystonia. J Neurol Sci. 2011; 308(1-2): 103–109.
  37. Charles D, Brashear A, Hauser RA, et al. CD 140 Study Group. Efficacy, tolerability, and immunogenicity of onabotulinumtoxina in a randomized, double-blind, placebo-controlled trial for cervical dystonia. Clin Neuropharmacol. 2012; 35(5): 208–214.
  38. Evidente VG, Fernandez HH, LeDoux MS, et al. A randomized, double-blind study of repeated incobotulinumtoxinA (Xeomin(®)) in cervical dystonia. J Neural Transm (Vienna). 2013; 120(12): 1699–1707.
  39. Tyślerowicz M, Kiedrzyńska W, Adamkiewicz B, et al. Cervical dystonia - improving the effectiveness of botulinum toxin therapy. Neurol Neurochir Pol. 2020; 54(3): 232–242.
  40. Jost WH, Biering-Sørensen Bo, Drużdż A, et al. Preferred muscles in cervical dystonia. Neurol Neurochir Pol. 2020; 54(3): 277–279.
  41. Jost WH, Tatu L, Pandey S, et al. Frequency of different subtypes of cervical dystonia: a prospective multicenter study according to Col-Cap concept. J Neural Transm (Vienna). 2020; 127(1): 45–50.
  42. Jost WH, Drużdż A, Pandey S, et al. Dose per muscle in cervical dystonia: pooled data from seven movement disorder centres. Neurol Neurochir Pol. 2021 [Epub ahead of print].
  43. Schinwelski MJ, Sitek EJ, Wąż P, et al. Prevalence and predictors of post-stroke spasticity and its impact on daily living and quality of life. Neurol Neurochir Pol. 2019; 53(6): 449–457.
  44. 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.
  45. Bakheit AM, Pittock S, Moore AP, et al. A randomized, double-blind, placebo-controlled study of the efficacy and safety of botulinum toxin type A in upper limb spasticity in patients with stroke. Eur J Neurol. 2001; 8(6): 559–565.
  46. Brashear A, Gordon MF, Elovic E, et al. Botox Post-Stroke Spasticity Study Group. 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.
  47. Childers MK, Brashear A, Jozefczyk P, et al. Dose-dependent response to intramuscular botulinum toxin type A for upper-limb spasticity in patients after a stroke. Arch Phys Med Rehabil. 2004; 85(7): 1063–1069.
  48. McCrory P, Turner-Stokes L, Baguley IJ, et al. Botulinum toxin A for treatment of upper limb spasticity following stroke: a multi-centre randomized placebo-controlled study of the effects on quality of life and other person-centred outcomes. J Rehabil Med. 2009; 41(7): 536–544.
  49. 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.
  50. Kaji R, Osako Y, Suyama K, et al. GSK1358820 Spasticity Study Group. Botulinum toxin type A in post-stroke upper limb spasticity. Curr Med Res Opin. 2010; 26(8): 1983–1992.
  51. Wolf SL, Milton SB, Reiss A, et al. Further assessment to determine the additive effect of botulinum toxin type A on an upper extremity exercise program to enhance function among individuals with chronic stroke but extensor capability. Arch Phys Med Rehabil. 2012; 93(4): 578–587.
  52. Marciniak CM, Harvey RL, Gagnon CM, et al. Does botulinum toxin type A decrease pain and lessen disability in hemiplegic survivors of stroke with shoulder pain and spasticity?: a randomized, double-blind, placebo-controlled trial. Am J Phys Med Rehabil. 2012; 91(12): 1007–1019.
  53. Rosales RL, Kong KHe, Goh KJ, et al. Botulinum toxin injection for hypertonicity of the upper extremity within 12 weeks after stroke: a randomized controlled trial. Neurorehabil Neural Repair. 2012; 26(7): 812–821.
  54. 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.
  55. Kaňovský P, Elovic EP, Munin MC, et al. Randomized, placebo-controlled trial of incobotulinumtoxina for upper-limb post-stroke spasticity. Muscle Nerve. 2016; 53(3): 415–421.
  56. Rosales R, Balcaitiene J, Berard H, et al. Early AbobotulinumtoxinA (Dysport®) in Post-Stroke Adult Upper Limb Spasticity: ONTIME Pilot Study. Toxins. 2018; 10(7): 253.
  57. Abo M, Shigematsu T, Hara H, et al. Efficacy and Safety of OnabotulinumtoxinA 400 Units in Patients with Post-Stroke Upper Limb Spasticity: Final Report of a Randomized, Double-Blind, Placebo-Controlled Trial with an Open-Label Extension Phase. Toxins (Basel). 2020; 12(2).
  58. Lindsay C, Ispoglou S, Helliwell B, et al. Can the early use of botulinum toxin in post stroke spasticity reduce contracture development? A randomised controlled trial. Clin Rehabil. 2020 [Epub ahead of print]: 269215520963855.
  59. Intiso D, Simone V, Bartolo M, et al. High Dosage of Botulinum Toxin Type A in Adult Subjects with Spasticity Following Acquired Central Nervous System Damage: Where Are We at? Toxins (Basel). 2020; 12(5).
  60. 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.
  61. Wohlfarth K, Schwandt I, Wegner F, et al. Biological activity of two botulinum toxin type A complexes (Dysport and Botox) in volunteers: a double-blind, randomized, dose-ranging study. J Neurol. 2008; 255(12): 1932–1939.
  62. 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.
  63. Gracies JM, Esquenazi A, Brashear A, et al. International AbobotulinumtoxinA Adult Lower Limb Spasticity Study Group. Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension. Neurology. 2017; 89(22): 2245–2253.
  64. Pittock SJ, Moore AP, Hardiman O, et al. A double-blind randomised placebo-controlled evaluation of three doses of botulinum toxin type A (Dysport) in the treatment of spastic equinovarus deformity after stroke. Cerebrovasc Dis. 2003; 15(4): 289–300.
  65. 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.
  66. Burbaud P, Wiart L, Dubos JL, et al. A randomised, double blind, placebo controlled trial of botulinum toxin in the treatment of spastic foot in hemiparetic patients. J Neurol Neurosurg Psychiatry. 1996; 61(3): 265–269.
  67. 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): 787–797.
  68. Mancini F, Sandrini G, Moglia A, et al. A randomised, double-blind, dose-ranging study to evaluate efficacy and safety of three doses of botulinum toxin type A (Botox) for the treatment of spastic foot. Neurol Sci. 2005; 26(1): 26–31.
  69. Picelli A, Tamburin S, Bonetti P, et al. Botulinum toxin type A injection into the gastrocnemius muscle for spastic equinus in adults with stroke: a randomized controlled trial comparing manual needle placement, electrical stimulation and ultrasonography-guided injection techniques. Am J Phys Med Rehabil. 2012; 91(11): 957–964.
  70. Fietzek UM, Kossmehl P, Schelosky L, et al. Early botulinum toxin treatment for spastic pes equinovarus--a randomized double-blind placebo-controlled study. Eur J Neurol. 2014; 21(8): 1089–1095.
  71. Santamato A, Micello MF, Panza F, et al. Safety and efficacy of incobotulinum toxin type A (NT 201-Xeomin) for the treatment of post-stroke lower limb spasticity: a prospective open-label study. Eur J Phys Rehabil Med. 2013; 49(4): 483–489.
  72. Brin MF, James C, Maltman J. Botulinum toxin type A products are not interchangeable: a review of the evidence. Biologics. 2014; 8: 227–241.
  73. Spiegel LL, Ostrem JL, Bledsoe IO. FDA Approvals and Consensus Guidelines for Botulinum Toxins in the Treatment of Dystonia. Toxins (Basel). 2020; 12(5).
  74. Simpson DM, Blitzer A, Brashear A, et al. So Y; Therapeutics and Technology Assessment Subcommittee of the American Academy of . 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. 2008; 70: 1699–706.
  75. Albanese A, Asmus F, Bhatia KP, et al. EFNS guidelines on diagnosis and treatment of primary dystonias. Eur J Neurol. 2011; 18(1): 5–18.
  76. 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.
  77. 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.
  78. Aoki KR, Ranoux D, Wissel J. Using translational medicine to understand clinical differences between botulinum toxin formulations. Eur J Neurol. 2006; 13 Suppl 4: 10–19.
  79. Simpson DM, Gracies JM, Graham HK, et al. Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Assessment: Botulinum neurotoxin for the treatment of spasticity (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008; 70(19): 1691–1698.
  80. Hefter H, Hartmann CJ, Kahlen U, et al. Clinical Improvement After Treatment With IncobotulinumtoxinA (XEOMIN®) in Patients With Cervical Dystonia Resistant to Botulinum Toxin Preparations Containing Complexing Proteins. Front Neurol. 2021; 12: 636590.



Neurologia i Neurochirurgia Polska