Dataset Information

IncobotulinumtoxinA for the treatment of lower-limb spasticity in children and adolescents with cerebral palsy: A phase 3 study.

ABSTRACT:

Purpose

Investigate the efficacy and safety of multipattern incobotulinumtoxinA injections in children/adolescents with lower-limb cerebral palsy (CP)-related spasticity.

Methods

Phase 3 double-blind study in children/adolescents (Gross Motor Function Classification System - Expanded and Revised I-V) with unilateral or bilateral spastic CP and Ashworth Scale (AS) plantar flexor (PF) scores ⩾ 2 randomized (1:1:2) to incobotulinumtoxinA (4, 12, 16 U/kg, maximum 100, 300, 400 U, respectively) for two 12- to 36-week injection cycles. Two clinical patterns were treated. Pes equinus (bilateral or unilateral) was mandatory; if unilateral, treatment included flexed knee or adducted thigh.

Endpoints

Primary: AS-PF change from baseline to 4 weeks; Coprimary: investigator-rated Global Impression of Change Scale (GICS)-PF at 4 weeks; Secondary: investigator's, patient's, and parent's/caregiver's GICS, Gross Motor Function Measure-66 (GMFM-66).

Results

Among 311 patients, AS-PF and AS scores in all treated clinical patterns improved from baseline to 4-weeks post-injection and cumulatively across injection cycles. GICS-PF and GICS scores confirmed global spasticity improvements. GMFM-66 scores indicated better motor function. No significant differences between doses were evident. Treatment was well-tolerated, with no unexpected treatment-related adverse events or neutralising antibody development.

Conclusion

Children/adolescents with lower-limb spasticity experienced multipattern benefits from incobotulinumtoxinA, which was safe and well-tolerated in doses up to 16 U/kg, maximum 400 U.

SUBMITTER: Heinen F

PROVIDER: S-EPMC8673523 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimTo assess the efficacy and safety of repeat abobotulinumtoxinA injections in reducing upper limb spasticity in children with cerebral palsy (CP).MethodThis was a double-blind, repeat-cycle study (NCT02106351) in children with CP (2-17y). Children were randomized to receive 2U/kg (control), 8U/kg, or 16U/kg abobotulinumtoxinA injections into the target muscle group (wrist or elbow flexors) and additional muscles alongside occupational therapy via a home-exercise therapy program (HETP; minimum five 15min sessions/wk). Children received 8U/kg or 16U/kg plus HETP in cycles 2 to 4.ResultsDuring cycle 1, 210 children (126 males, 84 females; mean age [SD] 9y [4y 5mo], range 2-17y; n=70/group) had at least one upper limb abobotulinumtoxinA injection and 209 complied with the HETP. At week 6 of cycle 1, children in the 8U/kg or 16U/kg groups had significantly lower Modified Ashworth scale scores versus the 2U/kg group (primary outcome: treatment differences of -0.4 [p=0.012] and -0.7 [p<0.001] respectively). All groups improved on Physician Global Assessment and children in all groups achieved their treatment goals at least as expected. Therapeutic benefits were sustained during cycles 2 to 4; muscular weakness was the only treatment-related adverse event reported in at least one child/group (4.3% and 5.7% vs 1.4% respectively).InterpretationTreatment with 8U/kg or 16U/kg abobotulinumtoxinA significantly reduced upper limb spasticity versus the 2U/kg control dose. Therapeutic benefits of abobotulinumtoxinA plus HETP were sustained with repeat treatment cycles.What this paper addsAbobotulinumtoxinA injections significantly reduced upper limb spasticity in children with cerebral palsy. Children treated with abobotulinumtoxinA and targeted home exercises showed global improvement and goal attainment. Benefits were sustained over 1 year with repeat cycles of abobotulinumtoxinA and home exercises. AbobotulinumtoxinA injections into the upper limb were well tolerated over 1 year.

Project description:BackgroundIn the current study, we applied a combination of non-invasive neuromodulation modalities concurrently with multiple stimulating electrodes. Specifically, we used transcranial pulsed current stimulation (tPCS) and transcutaneous electrical nerve stimulation (TENS) as a novel strategy for improving lower limb spasticity in children with spastic cerebral palsy (SCP) categorized on levels III-V of the Gross Motor Function Classification System (GMFCS) with minimal side effects.MethodsSixty-three SCP children aged 2-12 years, who were classified on levels III-V of the GMFCS were randomly assigned to one of two groups, resulting in 32 children in the experimental group and 31 children in the control group. The experimental group underwent a combination therapy of tPCS (400 Hz, 1 mA cerebello-cerebral stimulation) and TENS (400 Hz, max 10 mA) for 30 min, followed by 30 min of physiotherapy five times per week for 12 weeks. The control group underwent physiotherapy only 30 mins per day five times per week for 12 weeks. In total, all groups underwent 60 treatment sessions. The primary outcome measures were the Modified Ashworth Scale (MAS) and Modified Tardieu Scale (MTS). Evaluations were performed 3 days before and after treatment.ResultsWe found a significant improvement in MAS and MTS scores of the lower limbs in the experimental group compared to the control group in the hip adductors (Left: p = 0.002; Right: p = 0.002), hamstrings (Left: p = 0.001; Right: p < 0.001, and gastrocnemius (Left: p = 0.001; Right: p = 0.000). Moreover, MTS scores of R1, R2 and R2-R1 in left and right hip adduction, knee joint, and ankle joint all showed significant improvements (p ≤ 0.05). Analysis of MAS and MTS scores compared to baseline scores showed significant improvements in the experimental group but declines in the control group.ConclusionThese results are among the first to demonstrate that a combination of tPCS and TENS can significantly improve lower limb spasticity in SCP children classified on GMFCS levels III-V with minimal side effects, presenting a novel strategy for addressing spasticity challenges in children with severe SCP.Trial registrationChiCTR.org, ChiCTR1800020283, Registration: 22 December 2018 (URL: http://www.chictr.org.cn/showproj.aspx?proj=33953 ).

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