Repeated injection cycles with abobotulinumtoxinA, a botulinum toxin type A, are recommended
in current clinical guidelines as a treatment option for adults with upper limb spastic
paresis. However, the magnitude of the maximal therapeutic effect of repeated abobotulinumtoxinA
treatment across different efficacy parameters and the number of injection cycles
required to reach maximal effect remain to be elucidated. Here, we present a post
hoc exploratory analysis of a randomized, double-blind, placebo-controlled trial (12-24
weeks; NCT01313299) and open-label extension study (up to 12 months; NCT0131331),
in patients aged 18-80 years with hemiparesis for >= 6 months after stroke/traumatic
brain injury. Two inferential methods were used to assess the changes in efficacy
parameters after repeat abobotulinumtoxinA treatment cycles: Mixed Model Repeated
Measures analysis and Non-Linear Random Coefficients analysis. Using the latter model,
the expected maximal effect size (not placebo-controlled) and the number of treatment
cycles to reach 90% of this maximal effect were estimated. Treatment responses in
terms of passive and perceived parameters (i.e. modified Ashworth scale in primary
target muscle group, disability assessment scale for principal target for treatment
or limb position, and angle of catch at fast speed) were estimated to reach near-maximal
effect in two to three cycles. Near-maximal treatment effect for active parameters
(i.e. active range of motion against the resistance of extrinsic finger flexors and
active function, assessed by the Modified Frenchay Scale) was estimated to be reached
one to two cycles later. In contrast to most parameters, active function showed greater
improvements at Week 12 (estimated maximal change from baseline-modified Frenchay
Scale overall score: +0.8 (95% confidence interval, 0.6; 1.0) than at Week 4 (+0.6
[95% confidence interval, 0.4; 0.8]). Overall, the analyses suggest that repeated
treatment cycles with abobotulinumtoxinA in patients chronically affected with upper
limb spastic paresis allow them to relearn how to use the affected arm with now looser
antagonists. Future studies should assess active parameters as primary outcome measures
over repeated treatment cycles, and assess efficacy at the 12-week time-point of each
cycle, as the benefits of abobotulinumtoxinA may be underestimated in the studies
of insufficient duration.
