Objective: To assess the efficacy/safety of incobotulinumtoxinA for upper- and combined upper-/lower-limb spasticity in ambulant and non-ambulant children/adolescents with cerebral palsy (CP).
Background: Spastic CP is the most common pathophysiological motor type, and can affect both the upper and lower limbs in children.
Method: This randomized Phase 3 study (XARA; NCT02002884) had a double-blind main period (MP) and an open-label extension (OLEX) period. Enrolled patients were 2–17 years of age and had uni-/bilateral CP and Ashworth Scale (AS) scores ≥2 in main clinical target patterns (flexed elbow and/or flexed wrist). Patients were randomized (2:1:1) to 3 incobotulinumtoxinA dose groups in the MP (8, 6, 2 U/kg body weight [BW]; maximum 200, 150, 50 U/upper limb) with additional lower-limb injections (total body dose ≤16–20 U/kg BW [≤400–500 U], depending on Gross Motor Function Classification System [GMFCS] level). In the OLEX, patients received 3 more injection cycles (ICs), with doses per the 8 U/kg BW group. Outcomes included AS, Global Impression of Change Scale (GICS), and adverse events (AEs).
Results: 350 patients were treated (mean [SD] age 7.3 [4.4] years, 62.9% male, BW 25.0 [15.0] kg, 30.9% GMFCS IV–V). 281 (80.3%) completed the study, receiving 4 ICs. In the MP, AS scores for the upper-limb main clinical pattern significantly improved from baseline to Week 4 (p<0.0001, MMRM), with a significantly greater improvement in the 8 U/kg vs the 2 U/kg group (LS mean [SE]: –1.15 [0.056] vs –0.93 [0.078]; difference: –0.22 [0.091]; p=0.017, MMRM). Many patients were AS responders, with ≥1-point improvement from baseline to Week 4 (8 U/kg: 85.5%; 6 U/kg: 75.9%; 2 U/kg: 70.6%). Improvements in AS scores were seen in all treated upper-/lower-limb clinical patterns, and across all OLEX ICs. Investigator’s GICS scores confirmed improvements in upper-limb spasticity with all incobotulinumtoxinA doses (LS mean [SE]: 8 U/kg: 1.64 [0.062]; 6 U/kg: 1.44 [0.092]; 2 U/kg: 1.55 [0.083]). AE incidence did not increase with dose or repeated ICs.
Conclusion: In this large study, the efficacy/safety of incobotulinumtoxinA were demonstrated for muscle tone reduction in the multipattern treatment of spasticity in children/adolescents with CP.
Presented at TOXINS 2021 (Jan 16–17) and Physiatry 2021 (Feb 9–13).
To cite this abstract in AMA style:
E. Dabrowski, H. Chambers, D. Gaebler-Spira, M. Banach, P. Kaňovský, A. Hanschmann, M. Althaus, T. Geister, F. Heinen. Efficacy and safety of incobotulinumtoxinA for upper- or combined upper- and lower-limb spasticity in children/adolescents with cerebral palsy: the XARA study [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/efficacy-and-safety-of-incobotulinumtoxina-for-upper-or-combined-upper-and-lower-limb-spasticity-in-children-adolescents-with-cerebral-palsy-the-xara-study/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-and-safety-of-incobotulinumtoxina-for-upper-or-combined-upper-and-lower-limb-spasticity-in-children-adolescents-with-cerebral-palsy-the-xara-study/