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,
• MeSH
• Pain drug therapy   etiology   MeSH
• Botulinum Toxins, Type A * therapeutic use   MeSH
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Cerebral Palsy * complications   drug therapy   MeSH
• Neuromuscular Agents * therapeutic use   MeSH
• Muscle Spasticity drug therapy   etiology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Botulinum Toxins, Type A * MeSH
• incobotulinumtoxinA MeSH Browser
• Neuromuscular Agents * MeSH

PURPOSE: A large prospective database from three Phase 3 studies allowed the study of spasticity-related pain (SRP) in pediatric cerebral palsy (CP). METHODS: Baseline (pretreatment) SRP data occurring during different activities in children/adolescents (aged 2-17 years, ambulant/nonambulant) with uni-/bilateral spastic CP was obtained using the Questionnaire on Pain caused by Spasticity (QPS; six modules specific to spasticity level [lower limb (LL) or upper limb (UL)] and type of respondent [child/adolescent, interviewer, or parent/caregiver]). RESULTS: At baseline, 331 children/adolescents with LL- and 155 with UL-spasticity completed at least one key item of their modules; LL/UL QPS modules of parent/caregivers were at least partially completed (key items) by 841/444 parents/caregivers. SRP with at least one activity at baseline was self-reported in 81.9% /69.7% (LLs/ULs) of children/adolescents with spasticity. Parents/caregivers observed LL/UL SRP behaviors in 85.9% /77.7% of their children, with multiple body regions affected. SRP negatively affected the great majority of the children in various ways. Child/adolescent-reported mean SRP intensity and parent/caregiver-observed mean SRP behavior frequencies were higher for LLs than ULs, and the level of SRP increased with more physically demanding activities. CONCLUSION: These data suggest SRP is more common and intense in pediatric CP than generally thought, emphasizing the need for effective, long-term pain management.

• Keywords
• Botulinum toxin, all movement disorders, all pediatric, cerebral palsy, muscle spasticity, pain,
• MeSH
• Pain epidemiology   etiology   MeSH
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Cerebral Palsy * complications   epidemiology   MeSH
• Child, Preschool MeSH
• Prevalence MeSH
• Surveys and Questionnaires MeSH
• Muscle Spasticity * complications   etiology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Child, Preschool MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

PURPOSE: The open-label phase 3 "Treatment with IncobotulinumtoxinA in Movement Open-Label" (TIMO) study investigated longer-term safety and efficacy of incobotulinumtoxin A in children/adolescents with cerebral palsy (CP). METHODS: Patients on standard treatment, with unilateral or bilateral lower limb (LL) or combined upper limb (UL)/LL spasticity received four incobotulinumtoxinA injection cycles (16 or 20 Units/kg bodyweight total [maximum 400 or 500 Units] per cycle depending on ambulatory status/clinical pattern treated), each followed by 12-16 weeks' observation. Treatment for pes equinus was mandatory; flexed knee or adducted thigh were options for unilateral treatment and/or ULs for unilateral/bilateral treatment. The primary endpoint was safety; changes in Ashworth Scale and Gross Motor Function Measure-66 scores, and Global Impression of Change Scale scores at week 4 of each injection cycle were also evaluated. RESULTS: IncobotulinumtoxinA (≤500 Units for ≤98 weeks) was safe, well-tolerated, and effective across all endpoints for multipattern treatment of LL and combined LL/UL spasticity in ambulant/nonambulant children/adolescents with CP. Treatment effects increased with each injection cycle. No new/unexpected safety concerns were identified. CONCLUSION: IncobotulinumtoxinA showed a good safety and tolerability profile, with efficacy over multiple clinical presentations. As an adjunct treatment, it offers an effective, individualized treatment option for pediatric CP-related spasticity.

• Keywords
• Botulinum toxins, Type A, cerebral palsy, movement disorders, muscle spasticity, paediatric,
• MeSH
• Botulinum Toxins, Type A * adverse effects   MeSH
• Child MeSH
• Lower Extremity MeSH
• Humans MeSH
• Adolescent MeSH
• Cerebral Palsy * complications   drug therapy   MeSH
• Neuromuscular Agents * MeSH
• Muscle Spasticity drug therapy   etiology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Botulinum Toxins, Type A * MeSH
• incobotulinumtoxinA MeSH Browser
• Neuromuscular Agents * MeSH

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.

• Keywords
• Botulinum toxin, all movement disorders, all paediatric, cerebral palsy, incobotulinum, spasticity,
• MeSH
• Botulinum Toxins, Type A * adverse effects   MeSH
• Child MeSH
• Injections MeSH
• Humans MeSH
• Adolescent MeSH
• Cerebral Palsy * complications   drug therapy   MeSH
• Muscle Spasticity drug therapy   etiology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Botulinum Toxins, Type A * MeSH
• incobotulinumtoxinA MeSH Browser