Efficacy and Safety of OnabotulinumtoxinA for the Treatment of Pediatric Lower Limb Spasticity: Primary Results (S29.007)

Objective: To evaluate the safety and efficacy of onabotulinumtoxinA for lower limb spasticity/hypertonia in children with cerebral palsy. Background: Spasticity is a common finding in children with cerebral palsy, impairing function, worsening quality of life, and causing pain. Safety and efficacy of onabotulinumtoxinA treatment have been established in adults but not children. Design/Methods: In this phase 3, randomized, double-blind, placebo-controlled study (Clinicaltrials.gov identifier NCT01603628), children with cerebral palsy (2–≤17 years) with ankle plantar flexor Modified Ashworth Scale-Bohannon (MAS) ≥2 received onabotulinumtoxinA 8 U/kg, 4 U/kg, or placebo into ankle plantar flexors with standardized physiotherapy. The primary outcome was average change of spasticity in MAS score (Principle Muscle Group) at weeks 4 and 6. Secondary outcome measures included clinical global impression (CGI), Modified Tardieu Scale (MTS), and achievement of goal attainment score (GAS). Safety and tolerability of treatments were also assessed. Results: 384 patients were randomized: onabotulinumtoxinA, 254 (8 U/kg, 128; 4 U/kg, 126); placebo, 130. Eight patients (2.1%) discontinued, primarily for personal reasons (n=4). Mean (SD) age was 6.6 (3.8) years and patients were primarily white (60.6%) and Asian (29.9%). OnabotulinumtoxinA decreased spasticity; average MAS score at weeks 4 and 6 decreased 1.1 (8 U/kg) and 1.0 (4 U/kg); both significantly superior to placebo (−0.8, P P =0.023); onabotulinumtoxinA 4 U/kg, 1.5 ( P =0.229 vs placebo). Both onabotulinumtoxinA groups significantly improved active and passive GAS vs placebo; onabotulinumtoxinA 8 U/kg significantly improved measures of gait vs placebo. Rates of patients reporting ≥1 adverse event (AE) were similar across treatment groups: onabotulinumtoxinA, 43.3% (n=110); placebo, 49.2% (n=63). Serious AEs were reported by 1.2% (n=3) and 3.1% (n=4), respectively. No new safety concerns were identified. Conclusions: OnabotulinumtoxinA was safe and effective in treating lower limb spasticity in pediatric patients with cerebral palsy. Study Supported by: Allergan plc Disclosure: Dr. Kim has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan (consulting); LIH investment and Management Co, Ltd (teaching honorarium). Dr. Kim has received research support from Ipsen (PI for multicenter trial). Dr. Meilahn has nothing to disclose. Dr. Liu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan plc employee. Dr. Chambers has nothing to disclose. Dr. Dimitrova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan plc, employee. Dr. Dimitrova holds stock and/or stock options in Stock and stock options in Allergan plc, which sponsored research in which Dr. Dimitrova was involved as an investigator.