Ruber International Hospital, Madrid, Spain.
Bellvitge Hospital, Barcelona, Spain.
Epilepsy Behav. 2022 Jul;132:108711. doi: 10.1016/j.yebeh.2022.108711. Epub 2022 May 16.
Dravet Syndrome (DS) is a severe, developmental epileptic encephalopathy (DEE) that begins in infancy and is characterized by pharmaco-resistant epilepsy and neurodevelopmental delay. Despite available antiseizure medications (ASMs), there is a need for new therapeutic options with greater efficacy in reducing seizure frequency and with adequate safety and tolerability profiles. Fenfluramine is a new ASM for the treatment of seizures associated with DS as add-on therapy to other ASMs for patients aged 2 years and older. Fenfluramine decreases seizure frequency, prolongs periods of seizure freedom potentially helping to reduce risk of Sudden Unexpected Death in Epilepsy (SUDEP) and improves patient cognitive abilities positively impacting on patients' Quality of Life (QoL). Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine what represents value in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. The aim of this study was to determine the relative value contribution of fenfluramine for the treatment of DS in Spain using MCDA.
A literature review was performed to populate an adapted a MCDA framework for orphan-drug evaluation in Spain. A panel of ten Spanish experts, including neurologists, hospital pharmacists, patient representatives and decision-makers, scored four comparative evidence matrices. Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology.
Dravet syndrome is considered a severe, rare disease with significant unmet needs. Fenfluramine is perceived to have a higher efficacy profile than all available alternatives, with a better safety profile than stiripentol and topiramate and to provide improved QoL versus studied alternatives. Fenfluramine results in lower other medical costs in comparison with stiripentol and clobazam. Participants perceived that fenfluramine could lead to indirect costs savings compared to available alternatives due to its efficacy in controlling seizures. Overall, fenfluramine's therapeutic impact on patients with DS is considered high and supported by high-quality evidence.
Based on reflective MCDA, fenfluramine is considered to add greater benefit in terms of efficacy, safety and QoL when compared with available ASMs.
德拉韦综合征（DS）是一种严重的婴儿期起病的发育性癫痫脑病（DEE），其特征为药物难治性癫痫和神经发育迟缓。尽管有可用的抗癫痫药物（ASM），但仍需要新的治疗选择，这些选择需要具有更高的疗效，以降低癫痫发作频率，同时具有足够的安全性和耐受性。芬氟拉明是一种新的 ASM，用于治疗与 DS 相关的癫痫发作，作为附加疗法与其他 ASM 联合用于 2 岁及以上患者。芬氟拉明可降低癫痫发作频率，延长无癫痫发作的时间，从而可能降低癫痫猝死（SUDEP）的风险，并改善患者认知能力，从而对患者的生活质量（QoL）产生积极影响。反思性多准则决策分析（MCDA）方法可以确定在给定适应症中代表价值的是什么，考虑到医疗保健决策的所有相关标准，以透明和系统的方式从相关利益相关者的角度进行。本研究的目的是使用 MCDA 确定在西班牙使用芬氟拉明治疗 DS 的相对价值贡献。
进行了文献回顾，以填充适用于西班牙孤儿药物评估的 MCDA 框架。一个由 10 名西班牙专家组成的小组，包括神经病学家、医院药剂师、患者代表和决策者，对四个比较证据矩阵进行了评分。结果通过反思性 MCDA 讨论方法在一次小组会议上进行了分析和讨论。
德拉韦综合征被认为是一种严重的罕见疾病，存在重大未满足的需求。与所有现有替代药物相比，芬氟拉明被认为具有更高的疗效，与斯替戊醇和托吡酯相比具有更好的安全性，并提供了优于研究替代药物的 QoL。与斯替戊醇和氯巴占相比，芬氟拉明导致其他医疗费用降低。与现有替代药物相比，参与者认为芬氟拉明由于其控制癫痫发作的功效，可能会导致间接成本节省。总的来说，芬氟拉明对 DS 患者的治疗影响被认为是高的，并得到高质量证据的支持。
基于反思性 MCDA，与现有 ASM 相比，芬氟拉明在疗效、安全性和 QoL 方面被认为具有更大的益处。
