Comparative efficacy, safety, and cost-effectiveness of abobotulinumtoxinA and onabotulinumtoxinA in children with upper limb spasticity: a systematic literature review, indirect treatment comparison, and economic evaluation.

OBJECTIVE: The objective of this study was to compare clinical- and cost-effectiveness of type A botulinum toxin (BoNT-A) therapies for management of pediatric upper limb spasticity, including AbobotulinumtoxinA (aboBoNT-A) and Onabotulinumtoxin A (onaBoNT-A). METHODS: Systematic literature review and indirect treatment comparisons were conducted of randomized controlled trials reporting efficacy and safety outcomes. Efficacy was characterized by Modified Ashworth Scale (MAS) and Ashworth Scale (AS) up to 16-weeks post-injection. Results were used to inform a cost-effectiveness model with a 1-year time horizon, linking response rates with health-related quality-of-life (HRQoL) outcomes and costs from a UK perspective. Other data sources included in the cost-effectiveness model were drug unit costs, health care resource utilization based on UK physician survey, and HRQoL impacts of adverse events associated with oral anti-spasticity therapies. Results were characterized as cost per quality-adjusted life year and cost per responder. RESULTS: Six studies were included in evidence syntheses. There was a trend towards greater response rate for aboBoNT-A which resulted in improved HRQoL and lower annual costs compared with onaBoNT-A. Safety outcomes were similar across BoNT-A therapies. In cost-effectiveness analysis, aboBoNT-A was an economically dominant therapy with respect to cost per quality-adjusted life year. The cost per responder at 1 year was estimated to be £39,056 for aboBoNT-A vs. £54,831 for onaBoNT-A. LIMITATIONS AND CONCLUSIONS: Based on observed safety and efficacy data, aboBoNT-A is estimated to result in higher treatment response and consequently increased quality-of-life and reduced costs, vs. onaBoNT-A in children with upper limb spasticity. Limitations to the study include study heterogeneity limited details available for onaBoNT-A studies (e.g. use of physical therapy), and limited availability of responder data. Where assumptions were required, they were made to be conservative towards aboBoN-A.

Can a modified interspinous spacer prevent instability in axial rotation and lateral bending? A biomechanical in vitro study resulting in a new idea.

BACKGROUND: Interspinous spacers are mainly used to treat lumbar spinal stenosis and facet arthrosis. Biomechanically, they stabilise in extension but do not compensate instability in axial rotation and lateral bending. It would therefore be desirable to have an interspinous spacer available, which provides for more stability also in these two planes. At the same time, the intervertebral disc should not completely be unloaded to keep it viable. To meet these requirements, a new version of the Coflex interspinous implant was developed, called "Coflex rivet", which can be more rigidly attached to the spinous processes. The aim was to investigate whether this new implant compensates instability but still allows some load to be transferred through the disc. METHODS: Twelve human lumbar spine segments were equally divided into two groups, one for Coflex rivet and one for the original Coflex implant. The specimens were tested for flexibility under pure moment loads in the three main planes. These tests were carried out in the intact condition, after creation of a destabilising defect and after insertion of either of the two implants. Before implantation, the interspinous spacers were equipped with strain gauges to measure the load transfer. FINDINGS: Compared to the defect condition, both implants had a strong stabilising effect in extension (P<0.05). Coflex rivet also strongly stabilised in flexion and to a smaller degree in lateral bending and axial rotation (P<0.05). In contrast, in these three loading directions, the original Coflex implant could not compensate the destabilising effect of the defect (P>0.05). The bending moments transferred through the implants were highest in extension and flexion. Yet, they were no more than 1.2 Nm in median. INTERPRETATION: The new Coflex rivet seems be a suitable option to compensate instability. Its biomechanical characteristics might even make it suitable as an adjunct to fusion, which would be a new indication for this type of implant.