Siddiqui Jamshaed, Bowditch Sally
FIECON, London, UK.
Jazz Pharmaceuticals UK Ltd., London, UK.
J Health Econ Outcomes Res. 2024 Dec 23;11(2):168-179. doi: 10.36469/001c.126071. eCollection 2024.
Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are severe, treatment-refractory, epileptic encephalopathies that often develop in infancy or early childhood. Since December 1, 2022, plant-derived highly purified cannabidiol (CBD) medicine (Epidyolex®; 100 mg/mL oral solution) has been reimbursed in the Netherlands for the adjunctive treatment of seizures associated with LGS or DS. To estimate the cost-effectiveness of CBD plus usual care vs usual care alone in patients with LGS or DS in the Netherlands. A cohort-based Markov model from a Dutch societal perspective, based on seizure frequency and seizure-free days, was developed for patients receiving CBD plus usual care (antiseizure medications, including clobazam) or usual care alone. Population characteristics, clinical inputs, and utility values were sourced from CBD clinical trials and quality-of-life studies. Drug acquisition, disease management, adverse events, and societal costs from published literature were included. A 2019/2020 price year in euros was used. The model used a mean dosage of 12 mg/kg/day, a lifetime (90-year) horizon, and a 3-month cycle length. Discount rates of 4.0% and 1.5% per annum were applied to costs and outcomes, respectively. Uncertainty was explored through deterministic and probabilistic sensitivity analyses. In patients with LGS, CBD plus usual care led to additional costs of €28 338 and increased quality-adjusted life-years (QALYs) of 1.318 compared with usual care alone. The incremental cost-effectiveness ratio of €21 493/QALY in LGS is below the willingness-to-pay threshold of €80 000/QALY in the Netherlands. In patients with DS, CBD plus usual care dominated usual care alone, with cost savings of €23 642 and increased QALYs of 0.868. The probability that CBD plus usual care is cost-effective in the Netherlands compared with usual care alone is 96% and 99% in patients with LGS and DS, respectively. Elicitation methods were used to address data gaps in model inputs (eg, healthcare resource utilization and utilities); Dutch clinical experts, sensitivity, and scenario analyses validated this approach. Based on a willingness-to-pay threshold of €80 000, the base case cost-utility analysis demonstrated the cost-effectiveness of CBD plus usual care in patients with treatment-refractory LGS or DS aged 2 years or older in the Netherlands.
伦诺克斯 - 加斯托综合征（LGS）和德雷维特综合征（DS）是严重的、治疗难治性癫痫性脑病，通常在婴儿期或幼儿期发病。自2022年12月1日起，植物源高纯度大麻二酚（CBD）药物（Epidyolex®；100毫克/毫升口服溶液）在荷兰已被纳入医保，用于辅助治疗与LGS或DS相关的癫痫发作。为评估在荷兰LGS或DS患者中，CBD联合常规治疗与单纯常规治疗相比的成本效益。从荷兰社会视角出发，基于癫痫发作频率和无癫痫发作天数，为接受CBD联合常规治疗（抗癫痫药物，包括氯巴占）或单纯常规治疗的患者建立了一个基于队列的马尔可夫模型。人群特征、临床数据和效用值来源于CBD临床试验和生活质量研究。纳入了已发表文献中的药物购置、疾病管理、不良事件和社会成本。采用2019/2020年欧元价格年份。该模型使用的平均剂量为12毫克/千克/天，时间跨度为终身（90年），周期长度为3个月。成本和结果的贴现率分别为每年4.0%和1.5%。通过确定性和概率敏感性分析探讨不确定性。在LGS患者中，与单纯常规治疗相比，CBD联合常规治疗导致额外成本28338欧元，质量调整生命年（QALYs）增加1.318。LGS中每QALY增量成本效益比为21493欧元，低于荷兰每QALY支付意愿阈值80000欧元。在DS患者中，CBD联合常规治疗优于单纯常规治疗，节省成本23642欧元，QALYs增加0.868。在荷兰，与单纯常规治疗相比，CBD联合常规治疗具有成本效益的概率在LGS患者中为96%，在DS患者中为99%。采用启发式方法解决模型输入中的数据缺口（如医疗资源利用和效用）；荷兰临床专家、敏感性分析和情景分析验证了该方法。基于80000欧元的支付意愿阈值，基础病例成本效用分析证明了在荷兰，CBD联合常规治疗对于2岁及以上难治性LGS或DS患者具有成本效益。
