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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 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. Abbreviated summary In this post hoc analysis of repeated abobotulinumtoxinA injection cycles in upper limb spastic paresis, Gracies et al. used statistical modelling to elucidate the maximal therapeutic effect of abobotulinumtoxinA. Notably, the number of injections required to reach this maximal effect was higher for active (e.g. active function) compared with passive (e.g. tone) parameters.

SUBMITTER: Gracies JM

PROVIDER: S-EPMC7850141 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Gracies Jean-Michel JM Jech Robert R Valkovic Peter P Marque Philippe P Vecchio Michele M Denes Zoltan Z Vilain Claire C Delafont Bruno B Picaut Philippe P

Brain communications 20201118 1

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 <i>post hoc</i> exploratory analysis of a randomized, double-bl ...[more]

PMID: 33543139

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Project description:Botulinum toxin-A (BoNT-A) is an effective treatment for cervical dystonia (CD) and spastic paresis (SP), but it requires in-depth knowledge of anatomy and injection techniques. The Ixcellence Network® is an educational programme to provide neurology, neuropaediatrics, and physical medicine and rehabilitation (PMR) specialists with access to best clinical practices and innovations regarding SP and CD management with BoNT-A. To assess the benefits of such educational programmes and identify unmet needs, a multidisciplinary scientific committee designed INPUT (INjection Practice, Usage & Training), an international multicentric survey describing training and practices among this trained and experienced population. A self-completed questionnaire was sent online to 553 trainees and 14 trainers from the Ixcellence Network®. Among the 131 respondents, 92% specialized in PMR (48%) or neurology (44%), with a mean experience of 15.5 years in their clinical fields and 10.9 years of BoNT-A injection. Most of them (98%) reported having received training before performing their first BoNT-A injection and attending specific courses on how to perform it without any instrumental guidance (76%), and with ultrasound (73%), electrical stimulation (44%) or electromyography (41%). In terms of practices, 92% of respondents reported using at least one guidance technique while injecting, with ultrasound being the most used technique (48%). Attending specific courses was significantly associated with greater self-confidence and use, e.g. for injection with ultrasound, mean self-confidence, on a scale from 1 (not confident) to 10 (fully confident), was 7.9 for trained respondents (vs 4.0 for untrained respondents, p < 0.001) of whom 70% stated that they used this technique regularly or systematically (vs. 11% of untrained healthcare professionals (HCPs), p < 0.0001). Moreover, 84% of respondents reported having trained colleagues, residents or fellows through theoretical (70%) or practical teaching in individuals (80%) or in small groups (65%). Overall, 86% of respondents reported a notable increase over the past 5 years of the number of patients treated with BoNT-A. INPUT is the first international survey describing training and practices in SP and CD management of physicians who attended a dedicated educational programme. The results highlighted the importance of training for self-confidence, and the use of specific techniques and new approaches.

Project description:ObjectivesThe therapeutic effects of botulinum neurotoxin (BoNT) are well documented in upper limb spasticity. However, several factors may influence treatment efficacy, including targeting of neuromuscular junctions (NMJs). We examined whether NMJ-targeted BoNT injections were non-inferior, in terms of efficacy, to current injection practices.DesignOpen-label prospective evaluator-blinded study.SettingConducted across 20 medical centres in Denmark, Finland, Norway and Sweden (24 September 2012 to 11 March 2015).ParticipantsAged ˃18 years with upper limb spasticity (Modified Ashworth Scale [MAS] score of 2 or 3) following stroke or traumatic brain injury, had received ≥2 consecutive BoNT-A treatment cycles (the latest of which was abobotulinumtoxinA [aboBoNT-A]) and needed BoNT-A retreatment (same modality as previous cycle). Patients requiring aboBoNT-A doses >800units were excluded. In total, 88 patients were randomised (intention-to-treat [ITT] population), most were male (n=58/88, 65.9%) and 54/88 (61.4%) completed the study (per protocol [PP] population).InterventionsRandomisation (1:1) to receive a single dose of aboBoNT-A (≤800 U) according to either current clinical practice (300 U/mL) or as an NMJ-targeted injection (100 U/mL).Primary outcome measureProportion of patients with a ≥1 level reduction from baseline in MAS score at week 4 post-injection (responders).ResultsIn the ITT population, the proportion of responders at elbow flexors was 72.7% in the current practice group and 56.8% in the NMJ-targeted group (adjusted difference -0.1673 [95% CIs: -0.3630 to 0.0284]; p=0.0986). Similar results were observed in the PP population (69.0% vs 68.0%, respectively, adjusted difference 0.0707 [-0.1948 to 0.3362]; p=0.6052).ConclusionsOwing to the limited number of participants, non-inferiority of NMJ-targeted injections could not be determined. However, there was no statistical difference between groups. Larger studies are needed confirm whether the two techniques offer comparable efficacy.Trial registration numberNCT01682148.

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

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

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