IncobotulinumtoxinA Efficacy/Safety in Upper-Limb Spasticity in Pediatric Cerebral Palsy: Randomized Controlled Trial

Pediatr Neurol. 2021 Oct;123:10-20. doi: 10.1016/j.pediatrneurol.2021.05.014. Epub 2021 May 21.


Background: This randomized phase 3 study with double-blind main period (MP) and open-label extension (OLEX; NCT02002884) assessed incobotulinumtoxinA safety and efficacy for pediatric upper-limb spasticity treatment in ambulant/nonambulant (Gross Motor Function Classification System [GMFCS] I-V) patients, with the option of combined upper- and lower-limb treatment.

Methods: Patients were aged two to 17 years with unilateral or bilateral spastic cerebral palsy (CP) and Ashworth Scale (AS) score ≥2 in treatment-selected clinical patterns. In the MP, patients were randomized (2:1:1) to incobotulinumtoxinA 8, 6, or 2 U/kg body weight (maximum 200, 150, 50 U/upper limb), with optional lower-limb injections in one of five topographical distributions (total body dose ≤16 to 20 U/kg, maximum 400 to 500 U, depending on body weight and GMFCS level). In the OLEX, patients received three further treatment cycles, at the highest MP doses (8 U/kg/upper limb group). Outcomes included AS, Global Impression of Change Scale (GICS), and adverse events (AEs).

Results: AS scores improved from baseline to week 4 in all MP dose groups (n = 350); patients in the incobotulinumtoxinA 8 U/kg group had significantly greater spasticity improvements versus the 2 U/kg group (least-squares mean [standard error] for upper-limb main clinical target pattern -1.15 [0.06] versus -0.93 [0.08]; P = 0.017). Investigator's, child/adolescent's, and parent/caregiver's GICS scores showed improvements in all groups. Treatment benefits were sustained over further treatment cycles. AE incidence did not increase with dose or repeated treatment across GMFCS levels.

Conclusions: Data provide evidence for sustained efficacy and safety of multipattern incobotulinumtoxinA treatment in children and adolescents with upper-limb spasticity.

Keywords: Botulinum neurotoxin A; Cerebral palsy; IncobotulinumtoxinA; Multipattern treatment; Pediatric; Spasticity.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Botulinum Toxins, Type A / administration & dosage
  • Botulinum Toxins, Type A / adverse effects
  • Botulinum Toxins, Type A / pharmacology*
  • Cerebral Palsy / complications
  • Cerebral Palsy / drug therapy*
  • Child
  • Child, Preschool
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Muscle Spasticity / drug therapy*
  • Muscle Spasticity / etiology
  • Muscle Spasticity / physiopathology*
  • Neuromuscular Agents / administration & dosage
  • Neuromuscular Agents / adverse effects
  • Neuromuscular Agents / pharmacology*
  • Outcome Assessment, Health Care
  • Upper Extremity / physiopathology*


  • Neuromuscular Agents
  • Botulinum Toxins, Type A
  • incobotulinumtoxinA

Associated data