open access
Safety and efficacy of Botulinum toxin type A preparations in cerebral palsy — an evidence-based review
Affiliations- 1. Mazovian Neuropsychiatry Center, Limited Liability Company, Neuro Rehabilitation Department, Movement Analysis Lab., Zagórze, Poland, Zagorze n. Warsaw, 05-462 Wiazowna, Poland
- Dpt. of Neurology&Stroke, St. Adalbert Hospital, Al. Jana Pawła II 50, 80-462 Gdańsk, Poland
open access
Abstract
The introduction of botulinum toxin more than 25 years ago for the management of paediatric lower and upper limb hypertonia has been a major advance. BoNT-A as a part of multimodal treatment supports motor development and improves function disturbed by spasticity or hypertonia. The aim of this paper was to compare the efficacy and safety of three major BoNT-A preparations present on the market: abo-, inco-, and onaobotulinumtoxinA in the treatment of children with cerebral palsy. Based on an analysis of the available literature, all three preparations have been established to reduce hypertonia in the upper and lower extremities, with some conflicting evidence regarding function. There were no differences in treatment safety, with a low incidence of adverse events which were mostly temporary and mild. Any form of universal conversion ratio between all preparations is not recommended.
Abstract
The introduction of botulinum toxin more than 25 years ago for the management of paediatric lower and upper limb hypertonia has been a major advance. BoNT-A as a part of multimodal treatment supports motor development and improves function disturbed by spasticity or hypertonia. The aim of this paper was to compare the efficacy and safety of three major BoNT-A preparations present on the market: abo-, inco-, and onaobotulinumtoxinA in the treatment of children with cerebral palsy. Based on an analysis of the available literature, all three preparations have been established to reduce hypertonia in the upper and lower extremities, with some conflicting evidence regarding function. There were no differences in treatment safety, with a low incidence of adverse events which were mostly temporary and mild. Any form of universal conversion ratio between all preparations is not recommended.
Keywords
botulinum toxin, cerebral palsy
About this articleTitle
Safety and efficacy of Botulinum toxin type A preparations in cerebral palsy — an evidence-based review
Journal
Neurologia i Neurochirurgia Polska
Issue
Article type
Review Article
Pages
158-164
Published online
2021-04-16
Page views
1996
Article views/downloads
1488
DOI
Pubmed
Bibliographic record
Neurol Neurochir Pol 2021;55(2):158-164.
Keywords
botulinum toxin
cerebral palsy
Authors
Marcin Bonikowski
Jarosław Sławek
References (50)- Rosenbaum P, Paneth N, Leviton A, et al. A report: the definition and classification of cerebral palsy April 2006. Dev Med Child Neurol Suppl. 2007; 109: 8–14.
- Oskoui M, Coutinho F, Dykeman J, et al. An update on the prevalence of cerebral palsy: a systematic review and meta-analysis. Dev Med Child Neurol. 2013; 55(6): 509–519.
- Sanger TD, Delgado MR, Gaebler-Spira D, et al. Task Force on Childhood Motor Disorders. Classification and definition of disorders causing hypertonia in childhood. Pediatrics. 2003; 111(1): e89–e97.
- Molenaers G, Van Campenhout A, Fagard K, et al. The use of botulinum toxin A in children with cerebral palsy, with a focus on the lower limb. J Child Orthop. 2010; 4(3): 183–195.
- Strobl W, Theologis T, Brunner R, et al. Best clinical practice in botulinum toxin treatment for children with cerebral palsy. Toxins (Basel). 2015; 7(5): 1629–1648.
- Koman LA, Mooney JF, Smith B, et al. Management of cerebral palsy with botulinum-A toxin: preliminary investigation. J Pediatr Orthop. 1993; 13(4): 489–495.
- Cosgrove AP, Corry IS, Graham HK. Botulinum toxin in the management of the lower limb in cerebral palsy. Dev Med Child Neurol. 1994; 36(5): 386–396.
- Koman LA, Mooney JF, Smith BP, et al. Management of spasticity in cerebral palsy with botulinum-A toxin: report of a preliminary, randomized, double-blind trial. J Pediatr Orthop. 1994; 14(3): 299–303.
- Corry IS, Cosgrove AP, Duffy CM, et al. Botulinum toxin A in hamstring spasticity. Gait Posture. 1999; 10(3): 206–210.
- Mall V, Heinen F, Kirschner J, et al. Evaluation of botulinum toxin A therapy in children with adductor spasm by gross motor function measure. J Child Neurol. 2000; 15(4): 214–217.
- Molenaers G, Desloovere K, Fabry G, et al. The effects of quantitative gait assessment and botulinum toxin a on musculoskeletal surgery in children with cerebral palsy. J Bone Joint Surg Am. 2006; 88(1): 161–170.
- Scholtes VA, Dallmeijer AJ, Knol DL, et al. The combined effect of lower-limb multilevel botulinum toxin type a and comprehensive rehabilitation on mobility in children with cerebral palsy: a randomized clinical trial. Arch Phys Med Rehabil. 2006; 87(12): 1551–1558.
- Delgado MR, Hirtz D, Aisen M, et al. Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Practice parameter: pharmacologic treatment of spasticity in children and adolescents with cerebral palsy (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2010; 74(4): 336–343.
- Sutherland DH, Kaufman KR, Wyatt MP, et al. Double-blind study of botulinum A toxin injections into the gastrocnemius muscle in patients with cerebral palsy. Gait Posture. 1999; 10(1): 1–9.
- Koman LA, Mooney JF, Smith BP, et al. Botulinum toxin type A neuromuscular blockade in the treatment of lower extremity spasticity in cerebral palsy: a randomized, double-blind, placebo-controlled trial. BOTOX Study Group. J Pediatr Orthop. 2000; 20(1): 108–115.
- Ubhi T, Bhakta BB, Ives HL, et al. Randomised double blind placebo controlled trial of the effect of botulinum toxin on walking in cerebral palsy. Arch Dis Child. 2000; 83(6): 481–487.
- Baker R, Jasinski M, Maciag-Tymecka I, et al. Botulinum toxin treatment of spasticity in diplegic cerebral palsy: a randomized, double-blind, placebo-controlled, dose-ranging study. Dev Med Child Neurol. 2002; 44(10): 666–675.
- Kaňovský P, Bares M, Severa S, et al. Functional benefit of botulinum toxin (Dysport®) in the treatment of dynamic equinus cerebral palsy spasticity: a prospective, multicentre, double-blind, placebo-controlled study. Ceska a Slovenska Neurologie a Neurochirurgie. 2004; 67: 16–23.
- Ackman JD, Russman BS, Thomas SS, et al. Shriners Hospitals BTX-A Study Group. Comparing botulinum toxin A with casting for treatment of dynamic equinus in children with cerebral palsy. Dev Med Child Neurol. 2005; 47(9): 620–627.
- Bjornson K, Hays R, Graubert C, et al. Botulinum toxin for spasticity in children with cerebral palsy: a comprehensive evaluation. Pediatrics. 2007; 120(1): 49–58.
- Moore AP, Ade-Hall RA, Smith CT, et al. Two-year placebo-controlled trial of botulinum toxin A for leg spasticity in cerebral palsy. Neurology. 2008; 71(2): 122–128.
- Delgado MR, Tilton A, Russman B, et al. AbobotulinumtoxinA for Equinus Foot Deformity in Cerebral Palsy: A Randomized Controlled Trial. Pediatrics. 2016; 137(2): e20152830.
- Corry IS, Cosgrove AP, Walsh EG, et al. Botulinum toxin A in the hemiplegic upper limb: a double-blind trial. Dev Med Child Neurol. 1997; 39(3): 185–193.
- Koman LA, Smith BP, Williams R, et al. Upper extremity spasticity in children with cerebral palsy: a randomized, double-blind, placebo-controlled study of the short-term outcomes of treatment with botulinum A toxin. J Hand Surg Am. 2013; 38(3): 435–46.e1.
- Ferrari A, Maoret AR, Muzzini S, et al. A randomized trial of upper limb botulimun toxin versus placebo injection, combined with physiotherapy, in children with hemiplegia. Res Dev Disabil. 2014; 35(10): 2505–2513.
- Blumetti FC, Belloti JC, Tamaoki MJs, et al. Botulinum toxin type A in the treatment of lower limb spasticity in children with cerebral palsy. Cochrane Database Syst Rev. 2019 [Epub ahead of print]; 10: CD001408.
- Farag SM, Mohammed MO, El-Sobky TA, et al. Botulinum Toxin A Injection in Treatment of Upper Limb Spasticity in Children with Cerebral Palsy: A Systematic Review of Randomized Controlled Trials. JBJS Rev. 2020; 8(3): e0119.
- Pin TW, Elmasry J, Lewis J. Efficacy of botulinum toxin A in children with cerebral palsy in Gross Motor Function Classification System levels IV and V: a systematic review. Dev Med Child Neurol. 2013; 55(4): 304–313.
- Novak I, Morgan C, Fahey M, et al. State of the Evidence Traffic Lights 2019: Systematic Review of Interventions for Preventing and Treating Children with Cerebral Palsy. Curr Neurol Neurosci Rep. 2020; 20(2): 3.
- Albavera-Hernández C, Rodríguez JM, Idrovo AJ. Safety of botulinum toxin type A among children with spasticity secondary to cerebral palsy: a systematic review of randomized clinical trials. Clin Rehabil. 2009; 23(5): 394–407.
- Papavasiliou AS, Nikaina I, Foska K, et al. Safety of botulinum toxin A in children and adolescents with cerebral palsy in a pragmatic setting. Toxins (Basel). 2013; 5(3): 524–536.
- Bakheit AM, Severa S, Cosgrove A, et al. Safety profile and efficacy of botulinum toxin A (Dysport) in children with muscle spasticity. Dev Med Child Neurol. 2001; 43(4): 234–238.
- Naumann M, Albanese A, Heinen F, et al. Safety and efficacy of botulinum toxin type A following long-term use. Eur J Neurol. 2006; 13 Suppl 4: 35–40.
- Corry IS, Cosgrove AP, Duffy CM, et al. Botulinum toxin A compared with stretching casts in the treatment of spastic equinus: a randomised prospective trial. J Pediatr Orthop. 1998; 18(3): 304–311.
- Fehlings D, Rang M, Glazier J, et al. An evaluation of botulinum-A toxin injections to improve upper extremity function in children with hemiplegic cerebral palsy. J Pediatr. 2000; 137(3): 331–337.
- Tedroff K, Befrits G, Tedroff CJ, et al. To switch from Botox to Dysport in children with CP, a real world, dose conversion, cost-effectiveness study. Eur J Paediatr Neurol. 2018; 22(3): 412–418.
- Dursun N, Akarsu M, Gokbel T, et al. Switching from onabotulinumtoxin-A to abobotulinumtoxin-A in children with cerebral palsy treated for spasticity: A retrospective safety and efficacy evaluation. J Rehabil Med. 2019; 51(5): 390–394.
- Carraro E, Trevisi E, Martinuzzi A. Safety profile of incobotulinum toxin A [Xeomin(®)] in gastrocnemious muscles injections in children with cerebral palsy: Randomized double-blind clinical trial. Eur J Paediatr Neurol. 2016; 20(4): 532–537.
- León-Valenzuela A, Palacios JS, Del Pino Algarrada R. IncobotulinumtoxinA for the treatment of spasticity in children with cerebral palsy - a retrospective case series focusing on dosing and tolerability. BMC Neurol. 2020; 20(1): 126.
- Delgado MR, Bonikowski M, Carranza J, et al. Safety and Efficacy of Repeat Open-Label AbobotulinumtoxinA Treatment in Pediatric Cerebral Palsy. J Child Neurol. 2017; 32(13): 1058–1064.
- Tilton A, Russman B, Aydin R, et al. AbobotulinumtoxinA (Dysport) Improves Function According to Goal Attainment in Children With Dynamic Equinus Due to Cerebral Palsy. J Child Neurol. 2017; 32(5): 482–487.
- Dursun N, Bonikowski M, Dabrowski E, et al. Efficacy of Repeat AbobotulinumtoxinA (Dysport®) Injections in Improving Gait in Children with Spastic Cerebral Palsy. Dev Neurorehabil. 2020; 23(6): 368–374.
- Delgado MR, Tilton A, Carranza-Del Río J, et al. Dysport in PUL study group. Efficacy and safety of abobotulinumtoxinA for upper limb spasticity in children with cerebral palsy: a randomized repeat-treatment study. Dev Med Child Neurol. 2021; 63(5): 592–600.
- Heinen F, Kaňovský P, Schroeder A, et al. Efficacy and safety of incobotulinumtoxinA for lower-limb spasticity in children and adolescents with cerebral palsy. Toxicon. 2018; 156: S44.
- Kaňovský P, Heinen F, Schroeder S, et al. Long-term safety and efficacy of incobotulinumtoxinA for lower- or combined upper- and lower-limb spasticity in children and adolescents with cerebral palsy. Toxicon. 2018; 156: S56.
- Dabrowski E, Chambers H, Gaebler-Spira D, et al. Efficacy and safety of incobotulinumtoxinA for upper- or combined upper- and lower-limb spasticity in children and adolescents with cerebral palsy: Results of the Phase 3 XARA study. Toxicon. 2021; 190: S14–S15.
- Banach M, Kaňovský P, Schroeder AS, et al. eister T, L, . Safety of incobotulinumtoxinA in multipattern treatment of upper- and lower-limb spasticity in children/adolescents with cerebral palsy: Pooled analysis of 3 large phase 3 studies, Toxicon 2021; Vol 190. ; 2021 (Supp. 1): S7.
- Kim H, Meilahn J, et al. Efficacy and safety of onabotulinumtoxina for the treatment of pediatric lower limb spasticity: primary results. Developmental Medicine & Child Neurology. 2018; 60: 33–33.
- Kim H, Racette B, Dunn C, et al. Lower limb injections of onabotulinumtoxinA: Improvement in gait and treatment goal achievement in pediatric patients with cerebral palsy. Toxicon. 2021; 190: S40–S41.
- F2 efficacy and safety of onabotulinumtoxina for the treatment of pediatric upper limb spasticity: primary results. Developmental Medicine & Child Neurology. 2018; 60: 33–34.
