Document Type

Conference Proceeding

Publication Date


Publication Title

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.




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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.