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

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). 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. 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. 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.本研究旨在比较A型肉毒杆菌毒素（BoNT-A）疗法治疗儿童上肢痉挛的临床有效性与成本效益，涉及阿泊肉毒杆菌毒素A（aboBoNT-A）与奥那肉毒杆菌毒素A（onaBoNT-A）两种制剂。 本研究通过系统文献综述与间接治疗比较，对报告有效性及安全性结局的随机对照试验进行分析。以注射后16周内的改良Ashworth量表（MAS）与Ashworth量表（AS）评分作为有效性评估指标。研究结果被用于构建为期1年时间跨度的成本效益模型，该模型从英国医疗体系视角出发，将治疗应答率与健康相关生活质量（HRQoL）结局及医疗成本相挂钩。成本效益模型纳入的其他数据来源包括：药品单位成本、基于英国医师调查的医疗资源利用情况，以及口服抗痉挛疗法相关不良事件对健康相关生活质量的影响。研究结局以每质量调整生命年成本与每应答者成本两种方式进行表征。 证据合成共纳入6项研究。相较于奥那肉毒杆菌毒素A（onaBoNT-A），阿泊肉毒杆菌毒素A（aboBoNT-A）呈现出更高治疗应答率的趋势，进而可改善健康相关生活质量并降低年度医疗成本。两种BoNT-A疗法的安全性结局无显著差异。成本效益分析结果显示，就每质量调整生命年成本而言，阿泊肉毒杆菌毒素A属于经济学优势疗法。经估算，治疗1年时每应答者成本为：阿泊肉毒杆菌毒素A约39056英镑，奥那肉毒杆菌毒素A约54831英镑。基于已观测到的有效性与安全性数据，在儿童上肢痉挛患者中，相较于奥那肉毒杆菌毒素A，阿泊肉毒杆菌毒素A可获得更高的治疗应答率，进而提升患者生活质量并降低医疗成本。 本研究存在以下局限性：纳入研究存在异质性，且奥那肉毒杆菌毒素A相关研究的可用细节有限（如物理治疗的使用情况），同时治疗应答率数据的可获得性不足。在需作出假设的场景中，所有假设均对阿泊肉毒杆菌毒素A持保守设定。