Absence of Neutralizing Antibody Formation During IncobotulinumtoxinA Treatement of Spasticity in Botulinum Toxin-Naive Children With Cerebral Palsy: Pooled Analysis of Three Phase 3 Studies
Developmental Medicine and Child Neurology
Introduction: The development of neutralizing antibodies (NAbs) has been linked to secondary non-response to botulinum neurotoxin type A (BoNT-A) injections. This may be of special concern when treating conditions like pediatric spasticity. We investigated NAb formation in three large Phase 3 studies with incobotulinumtoxinA, a BoNT-A lacking complexing proteins, in children/adolescents with cerebral palsy (CP).
Patients and methods: Patients with lower-limb (LL), upper-limb (UL), or combined LL/UL spasticity (2–17 years; uni- or bilateral CP; Ashworth Scale score ≥2 in clinical patterns for treatment) received total body weight incobotulinumtoxinA ≤16–20 U/kg (max. 400–500 U) depending on the study (TIM: NCT01893411; TIMO: NCT01905683; XARA: NCT02002884) and Gross Motor Function Classification System level I–V, for up to six injection cycles (ICs). Occurrence of NAbs against BoNT-A was investigated in those ≥21 kg at screening and end of study. Blood samples were analyzed using a fluorescence immunoassay (FIA) for antibodies; positive samples were tested for NAbs using a hemidiaphragm assay.
Results: 907 patients received treatment. 386/403 (95.8%) and 318/422 (75.4%) with bodyweight ≥21 kg were tested using FIA at screening and end of study, respectively. 150/403 (37.2%) and 167/422 (39.6%) were toxin-naïve. Eleven patients tested positive for NAbs at screening and/or end of study, all of whom had previously been treated with other BoNT-As (onabotulinumtoxinA/abobotulinumtoxinA). No patient developed a secondary non-response to incobotulinumtoxinA. No toxin-naïve patients developed NAbs after incobotulinumtoxinA treatment.
Conclusions: NAb formation was not observed in toxin-naïve children/adolescents with CP treated with up to six ICs of incobotulinumtoxinA.
Chambers H, Kanovsky P, Schroeder AS, Dabrowski E, Geister T, Hanschmann A, et al. Absence of neutralizing antibody formation during incobotulinumtoxinA treatment of spasticity in botulinum toxin-naive children with cerebral palsy: pooled analysis of three phase 3 studies. Dev Med Child Neurol. 2022 May; 64(Suppl 3):89. doi:10.1111/dmcn.15215.
34th Annual Meeting of the European Academy of Childhood Disability, EACD 2022, May 18-21, 2022, Barcelona, Spain.
Association of Academic Physiatrists Annual Meeting, Physiatry '22, May 24-28, 2022, New Orleans, LA. Am J Phys Med Rehab. 2022 Jul;101(Suppl 7):A158-A159.