Introduction: Primary endpoint analysis of this phase 3 study confirmed abobotulinumtoxinA (aboBoNT-A 8 U/kg and 16 U/kg) significantly reduced hypertonia versus the 2 U/kg low-dose control and was generally well tolerated (Delgado, et al, 2021). However, the impact of previous botulinum neurotoxin (BoNT) injections on treatment outcomes remains largely unexplored.
Methods: We present subgroup analyses of a phase 3 study conducted in children (aged 2-17) with cerebral palsy (Gross Motor Function Classification System [GMFCS] Levels I-IV) and spasticity in ≥1 upper limb. In the first treatment cycle, 210 children were randomized to treatment with aboBoNT-A 2 U/kg, 8 U/kg or 16 U/kg into the primary target muscle group (PTMG; elbow or wrist flexors) and additional upper limb muscles. Children could be naïve to BoNT treatment or previously treated (with any BoNT formulation).
Results: In the modified intent-to-treat (mITT) population, 138 children had been previously treated with a BoNT formulation, and 70 children were new to treatment. At Week 6, previously treated children showed mean reductions (±SD in modified Ashworth scale (MASPTMG) scores of -1.4 ±1.0 in the 2 U/kg (n=45), -1.9 ±0.9 in the 8 U/kg (n=47), and -2.0 ±1.0 in the 16 U/kg (n=46) groups vs baseline. Children who were BoNT-naïve showed MASPTMG reductions of -1.5 ±1.2 (n=24), -2.0 ±1.3 (n=22), and -2.7 ±0.7 (n=24), respectively. Treatment differences were significant vs the control group for both subgroups treated with aboBoNT-A 16 U/kg and for the previously treated subgroup who received 8 U/kg. All children (all groups) showed improvement on the Physician Global Assessment. For this global assessment, the magnitude of improvement was slightly better for BoNT-naïve children in the 8 U/kg group than in other groups (2.3 vs 1.7-2.0 grade improvements in other subgroups). Adverse events during Cycle 1 (combined doses) were reported in a similar proportion of BoNT-naïve (52.8%) and previously treated (58.0%) children and most were considered unrelated to treatment. Eight children who had all been previously treated with BoNT reported experiencing muscular weakness.
Conclusions: These results demonstrate similar aboBoNT-A efficacy and safety profiles in children with upper limb spasticity who are new to BoNT treatment compared to those previously treated.
Dabrowski E, Delgado MR, Oleszek J, Dursun N, Del-Rio JC, Bonikowski M, et al AbobotulinumtoxinA efficacy and safety in children with upper limb spasticity previously treated with botulinum toxin. Toxicon. 2022 July; 214(Suppl 1):S14-S15.