Spasticity-related pain in children/adolescents with cerebral palsy. Part 2: IncobotulinumtoxinA efficacy results from a pooled analysis

Abstract

Purpose: This pooled analysis of data from three Phase 3 studies investigated the effects of incobotulinumtoxinA on spasticity-related pain (SRP) in children/adolescents with uni-/bilateral cerebral palsy (CP).

Methods: Children/adolescents (ambulant and non-ambulant) were evaluated for SRP on increasingly difficult activities/tasks 4 weeks after each of four incobotulinumtoxinA injection cycles (ICs) using the Questionnaire on Pain caused by Spasticity (QPS; six modules specific to lower limb [LL] or upper limb [UL] spasticity and respondent type [child/adolescent, interviewer, or parent/caregiver]). IncobotulinumtoxinA doses were personalized, with all doses pooled for analysis.

Results: QPS key item responses were available from 331 and 155 children/adolescents with LL- and UL-spasticity, respectively, and 841/444 (LL/UL) of their parents/caregivers. IncobotulinumtoxinA efficacy was evident with the first IC. Efficacy was sustained and became more robust with further subsequent ICs. By Week 4 of the last (i.e. fourth) IC, 33.8-53.3% of children/adolescents reported complete SRP relief from their baseline pain for respective QPS items. Children/adolescents reported reductions in mean LL SRP intensity at levels that surpassed clinically meaningful thresholds. Similarly, parents/caregivers observed complete SRP relief and less frequent SRP with incobotulinumtoxinA. Similar results were found for UL SRP.

Conclusion: These findings indicate that incobotulinumtoxinA could bring considerable benefit to children/adolescents with spasticity by reducing SRP, even during strenuous activities.

Keywords: Botulinum toxin; all movement disorders; all pediatric; cerebral palsy; muscle spasticity; pain.

Fig. 1

A: Study designs of TIM, TIMO, and XARA^a. B: Summary of clinical treatment patterns for 1) LL (TIM, TIMO, and XARA) and 2) UL (XARA and TIMO). ^aFor full details of the TIM, TIMO, and XARA studies, see the primary publications of each study [20–22]. ^bPatients previously enrolled in TIM who then entered TIMO only provided data for the current pain analyses during TIM. ^cInjections were administered bilaterally for pes equinus or unilaterally for pes equinus with the addition of another LL site (either flexed knee or adducted thigh) in TIM [20], bilaterally for pes equinus with potential to add an UL site or unilaterally for pes equinus and another ipsilateral LL site with or without UL sites (with doses for some combinations of clinical pattern dependent on GMFCS-E&R level) in TIMO [21], or unilaterally/bilaterally to a main UL clinical target pattern (flexed elbow or wrist) and additional UL clinical patterns, with further optional bilateral and uni/bilateral LL injections in one of five topographical distributions (with doses for some combinations of clinical pattern dependent on GMFCS-E&R level) in XARA [22]. BW = body weight; GMFCS-E&R = Gross Motor Function Classification System Expanded and Revised; LL = lower limb; QPS = Questionnaire on Pain caused by Spasticity; TIM = Treatment with IncobotulinumtoxinA in Movement; TIMO = Treatment with IncobotulinumtoxinA in Movement Open-label; UL = upper limb; XARA = incobotulinumtoXinA in aRm treatment in cerebral pAlsy.

Fig. 2

The overall proportion of children with lower limb and upper limb cerebral palsy-related spasticity reporting any SRP on any QPS key item at baseline and at Week 4 of each of four incobotulinumtoxinA injections cycles according to children/adolescents and parents/caregivers^a. ^aThe decrease in the number of patients with LL spasticity after IC2 reflects the design and contribution to the pooled data of the TIM study, which included only two injection cycles. BL = baseline; IC = injection cycle; n/N = number of subjects reporting any SRP (on one or more of items 8, 9b, 10b, 11b, and 13b) per assessment visit/number of parent/caregiver QPS subjects evaluated for SRP per assessment visit; QPS = Questionnaire on Pain caused by Spasticity; SRP = spasticity-related pain; TIM = Treatment with IncobotulinumtoxinA in Movement.