Efficacy and safety of onabotulinumtoxinA with standardized physiotherapy for the treatment of pediatric lower limb spasticity: A randomized, placebo-controlled, phase III clinical trial

Abstract

BACKGROUND: Spasticity is common in cerebral palsy and can result in pain and diminished health-related quality of life. OBJECTIVE: To evaluate the safety and efficacy of onabotulinumtoxinA for lower limb spasticity treatment in children with cerebral palsy. METHODS: In this registrational phase 3, multinational, randomized, double-blind, placebo-controlled trial (NCT01603628), children (2–< 17 years) with cerebral palsy and ankle spasticity (Modified Ashworth Scale-Bohannon [MAS] score≥2) were randomized 1 : 1:1 to standardized physical therapy and onabotulinumtoxinA (4 or 8 U/kg), or placebo. Primary endpoint was average change from baseline at weeks 4 and 6 in MAS ankle score. Secondary endpoints included the Modified Tardieu Scale (MTS) and Global Attainment Scale (GAS). RESULTS: 381 participants were randomized. MAS scores averaged at weeks 4 and 6 were significantly reduced with both onabotulinumtoxinA doses (8 U/kg: –1.06, p = 0.010; 4 U/kg: –1.01, p = 0.033) versus placebo (–0.8). Significant improvements in average dynamic component of spasticity, measured by MTS, and in function, measured by GAS, were observed at several time points with both onabotulinumtoxinA doses versus placebo. Most adverse events were mild or moderate. CONCLUSIONS: OnabotulinumtoxinA was well tolerated and effective in reducing lower limb spasticity and improving functional outcomes versus placebo in children.

Estudos Multidisciplinares Sobre Saúde Da Criança E Do Adolescente

“…Após remoção dos artigos duplicados e leitura dos títulos e dos resumos, obteve-se um total de 16 artigos para análise. Observou-se que a utilização da TB associada à fisioterapia resulta em uma melhora da espasticidade (AYDIL et al, 2019;BOYACI et al, 2014), principalmente quando comparada ao uso da fisioterapia como recurso isolado (DIMITROVA et al, 2022;LIU et al, 2014;LIU et al, 2022;OKUR;UĞUR;ŞENEL, 2019). Isso pode ocorrer devido à ação intramuscular da TB, que bloqueia a liberação de acetilcolina na junção neuromuscular, levando à paralisia muscular temporária (FARAG et al, 2020).…”

Toxina Botulínica Associada À Fisioterapia No Manejo Das Alterações Físicas E Funcionais Em Crianças E Adolescentes Com Paralisia Cerebral

“…Após remoção dos artigos duplicados e leitura dos títulos e dos resumos, obteve-se um total de 16 artigos para análise. Observou-se que a utilização da TB associada à fisioterapia resulta em uma melhora da espasticidade (AYDIL et al, 2019;BOYACI et al, 2014), principalmente quando comparada ao uso da fisioterapia como recurso isolado (DIMITROVA et al, 2022;LIU et al, 2014;LIU et al, 2022;OKUR;UĞUR;ŞENEL, 2019). Isso pode ocorrer devido à ação intramuscular da TB, que bloqueia a liberação de acetilcolina na junção neuromuscular, levando à paralisia muscular temporária (FARAG et al, 2020).…”

The Role of Botulinum Toxin Type-A in Spasticity: Research Trends from a Bibliometric Analysis

“…OnabotulinumtoxinA’s journey in CP began with early trials in the 1990s, showing efficacy in reducing spasticity, and progressed through critical double-blind trials and comprehensive Phase 2 studies, affirming its safety and effectiveness in improving gait function [ 40 , 77 ]. Recent studies have reinforced the efficacy and safety of OnabotulinumtoxinA in treating both upper and lower limb spasticity in CP, after its first FDA approval in 2019 [ 78 , 79 ]. In parallel, the therapeutic potential of IncobotulinumtoxinA has been explored in a series of determining studies: the TIM (Treatment with IncobotulinumtoxinA in Movement) study [ 80 ], the XARA (incobotulinumtoXinA in aRm treatment in CP) [ 81 ] study, and the TIMO (Treatment with IncobotulinumtoxinA in Movement Open-Label) study [ 82 ].…”