Efficacy and safety of abobotulinumtoxinA for upper limb spasticity in children with cerebral palsy: a randomized repeat-treatment study

Abstract

Aim: To assess the efficacy and safety of repeat abobotulinumtoxinA injections in reducing upper limb spasticity in children with cerebral palsy (CP).

Method: This was a double-blind, repeat-cycle study (NCT02106351) in children with CP (2-17y). Children were randomized to receive 2U/kg (control), 8U/kg, or 16U/kg abobotulinumtoxinA injections into the target muscle group (wrist or elbow flexors) and additional muscles alongside occupational therapy via a home-exercise therapy program (HETP; minimum five 15min sessions/wk). Children received 8U/kg or 16U/kg plus HETP in cycles 2 to 4.

Results: During cycle 1, 210 children (126 males, 84 females; mean age [SD] 9y [4y 5mo], range 2-17y; n=70/group) had at least one upper limb abobotulinumtoxinA injection and 209 complied with the HETP. At week 6 of cycle 1, children in the 8U/kg or 16U/kg groups had significantly lower Modified Ashworth scale scores versus the 2U/kg group (primary outcome: treatment differences of -0.4 [p=0.012] and -0.7 [p<0.001] respectively). All groups improved on Physician Global Assessment and children in all groups achieved their treatment goals at least as expected. Therapeutic benefits were sustained during cycles 2 to 4; muscular weakness was the only treatment-related adverse event reported in at least one child/group (4.3% and 5.7% vs 1.4% respectively).

Interpretation: Treatment with 8U/kg or 16U/kg abobotulinumtoxinA significantly reduced upper limb spasticity versus the 2U/kg control dose. Therapeutic benefits of abobotulinumtoxinA plus HETP were sustained with repeat treatment cycles.

What this paper adds: AbobotulinumtoxinA injections significantly reduced upper limb spasticity in children with cerebral palsy. Children treated with abobotulinumtoxinA and targeted home exercises showed global improvement and goal attainment. Benefits were sustained over 1 year with repeat cycles of abobotulinumtoxinA and home exercises. AbobotulinumtoxinA injections into the upper limb were well tolerated over 1 year.

Conflict of interest statement

MRD, AT, JCR, ND, MB, RA, IM‐T, JO, and ED were investigators in Ipsen‐sponsored clinical trials, and they or their institutions received payment for participation. In addition, MRD reports personal fees from Ipsen, Allergan, and Kashiv Pharma for consultancy. AT reports research support and educational grants from Ipsen, and personal fees for consultancy from Ipsen. JCR reports personal fees for consultancy and speaking from Ipsen. ND reports research support from Ipsen, Allergan, and Merz, and personal fees for consultancy and speaking from Ipsen and Allergan. MB reports research support from Ipsen, Allergan, and Merz, and personal fees for consultancy and speaking from Ipsen and Allergan. RA and IM‐T have nothing further to report. JO reports consultancy fees for Ipsen and Allergan. ED reports personal fees from Ipsen and Allergan for speaking, Solstice Neurosciences for consultancy, and serves on a US speaker bureau. PP was employed by Ipsen at the time of study.

© 2020 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.

Figures

Figure 1

Treatment efficacy during cycle 1. (a) Least squares mean change in MASPTMGfrom baseline to weeks 6 and 16. (b) Percentage of children achieving an improvement of at least one grade in PGA at weeks 6 and 16. (c) GAS T scores at weeks 6 and 16. AboBoNT‐A, abobotulinumtoxinA; GAS, goal attainment scaling; MAS, Modified Ashworth scale; LS, least squares; PGA, Physician Global Assessment; PTMG, primary targeted muscle group; SE, standard error; TE, treatment effect.