When can maximal efficacy occur with repeat botulinum toxin injection in upper limb spastic paresis?

Abstract

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 randomised, 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 following stroke/traumatic brain injury. Two inferential methods were used to assess 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 2–3 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 1–2 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 [CI] 0.6; 1.0) than at Week 4 (+0.6 [95% CI 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 studies of insufficient duration.

A practical guide to botulinum neurotoxin treatment of shoulder spasticity 2: Injection techniques, outcome measurement scales, and case studies

“…When BoNT-A is introduced early after the onset of spasticity, pain reduction is rapid, being observed after a single BoNT-A injection ( 29 ). However, maximal efficacy in passive and active function in most patients comes later, after three to four injections ( 30 ).…”

Holoprosencephaly: The Disease and Its Related Disabilities

“…Botulinum toxin therapy, movement training, as well as speech rehabilitation, most often used in rehabilitation of acquired cerebrovascular lesion in adult, could be used to limit spasticity, improve muscles recruitment capacity, and treat speech disorders with cause disability in holoprosensephaly. [53][54][55][56][57][58]…”

At the Basis of Brain Malformations: Brain Plasticity, Developmental Neurobiology, and Considerations for Rehabilitation

“…80 The spastic component in the outcomes of brain injury could inhibit the rehabilitation activity to be practiced to stimulate plasticity and can be reduced through muscle lengthening exercises or through drugs that block neuromuscular transmission such as botulinum toxin, widely used in adult and child disabilities. 78,[80][81][82][83][84][85] Cerebral plasticity also participates in the recovery of other functions such as speech, which positively benefits from rehabilitation exercise. 79,86,87…”