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

Abstract

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.

• Authors: Edward Dabrowski, Henry G Chambers, Deborah Gaebler-Spira, Marta Banach, Petr Kaňovský, Hanna Dersch, Michael Althaus, Thorin L Geister, Florian Heinen
• Journal: Pediatric neurology (Pediatr Neurol) Vol. 123 Pg. 10-20 (10 2021) ISSN: 1873-5150 [Electronic] United States
• PMID: 34339951 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Neuromuscular Agents
• Botulinum Toxins, Type A
• incobotulinumtoxinA

Topics

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