Tempest Michael, Sapin Christophe, Beillat Maud, Robinson Paul, Treur Maarten
Pharmerit International, Marten Meesweg 107., 3068 AV Rotterdam, Netherlands,
J Ment Health Policy Econ. 2015 Dec;18(4):185-200.
Schizophrenia is a severe and debilitating psychiatric disorder. Pharmacological interventions aim to ameliorate symptoms and reduce the risk of relapse and costly hospitalisation. Despite the established efficacy of antipsychotic medication, compliance to treatment is poor, particularly with oral formulation. The emergence of long acting injectable (LAI) antipsychotic formulations in recent years has aimed to counteract the poor compliance rates observed and optimise long term patient outcomes.
To estimate the cost-effectiveness of aripiprazole once-monthly 400mg (AOM 400) vs. risperidone long acting injectable (RLAI), paliperidone long acting injectable (PLAI) and olanzapine long acting injectable (OLAI) in the maintenance treatment of chronic, stable schizophrenia patients in the United Kingdom.
A Markov model was developed to emulate the treatment pathway of a hypothetical cohort of patients initiating maintenance treatment with LAI antipsychotics. The economic analysis was conducted from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a 10 year time horizon. Efficacy and safety probabilities were derived from mixed treatment comparisons (MTCs) where possible. Analyses were conducted assuming pooled dosing from randomised clinical trials included in the MTCs.
The model estimates that AOM 400 improves clinical outcomes by reducing relapses per patient comparative to other LAIs over the model time horizon (2.38, 2.53, 2.70, and 2.67 for AOM 400, RLAI, PLAI and OLAI respectively). In the deterministic analysis, AOM 400 dominated PLAI and OLAI; an incremental cost-effectiveness ratio (ICER) of GBP 3,686 per QALY gained was observed against RLAI. Results from the univariate sensitivity analyses highlighted the probability and cost of relapse as main drivers for cost-effectiveness. In the probabilistic sensitivity analysis, AOM 400 demonstrated a marginally higher probability of being cost-effective (51%) than RLAI, PLAI and OLAI (48%, 1% and 0%, respectively) at a willingness to pay threshold of GBP 20,000.
The model was built to accommodate results of an adjusted MTC analysis. Furthermore the model effectively captures repercussions of deteriorating compliance to treatment by incorporating three levels of compliance with elevated risks of relapse for partial compliance and non-compliance. Limitations of the analysis include the limited number of studies incorporated in the MTC, the extrapolation of short term clinical data and the exclusion of the wider societal burden.
Comparative to other atypical antipsychotics, AOM 400 represents value for money in the maintenance treatment of chronic, stable schizophrenia; however, in light of the PSA findings and comparable cost-effectiveness (i.e. against RLAI), the product profile and wider benefits of the respective treatments must be taken into account when prescribing antipsychotics.
Future research should assess the use of LAI antipsychotics earlier in the disease course of schizophrenia to see whether improved compliance and outcomes shortly following the onset of psychosis has the potential to alter the disease trajectory. Moreover it should be assessed whether changes in the disease trajectory can alleviate cost and resource pressures placed on national health services.
精神分裂症是一种严重且使人衰弱的精神疾病。药物干预旨在改善症状，降低复发风险以及昂贵的住院费用。尽管抗精神病药物已证实有效，但治疗依从性较差，尤其是口服制剂。近年来长效注射（LAI）抗精神病制剂的出现旨在应对观察到的低依从率，并优化患者长期治疗效果。
评估在英国慢性稳定型精神分裂症患者维持治疗中，阿立哌唑每月一次400mg（AOM 400）与利培酮长效注射剂（RLAI）、帕利哌酮长效注射剂（PLAI）及奥氮平长效注射剂（OLAI）相比的成本效益。
建立马尔可夫模型以模拟一组开始使用LAI抗精神病药物进行维持治疗的假设患者的治疗路径。从英国国家医疗服务体系（NHS）和个人社会服务（PSS）的角度，在10年时间范围内进行经济分析。疗效和安全性概率尽可能从混合治疗比较（MTC）中得出。分析假设采用MTC中纳入的随机临床试验的合并剂量。
模型估计，在模型时间范围内，与其他长效注射剂相比，AOM 400通过降低每位患者的复发率改善了临床结局（AOM 400、RLAI、PLAI和OLAI的复发率分别为2.38、2.53、2.70和2.67）。在确定性分析中，AOM 400优于PLAI和OLAI；与RLAI相比，每获得一个质量调整生命年（QALY）的增量成本效益比（ICER）为3686英镑。单因素敏感性分析结果突出了复发概率和成本是成本效益的主要驱动因素。在概率敏感性分析中，在支付意愿阈值为20000英镑时，AOM 400具有成本效益的概率（51%）略高于RLAI、PLAI和OLAI（分别为48%、1%和0%）。
该模型旨在纳入调整后的MTC分析结果。此外，该模型通过纳入三个依从性水平，有效捕捉了治疗依从性下降的影响，部分依从和不依从会增加复发风险。分析的局限性包括MTC中纳入的研究数量有限、短期临床数据的外推以及未考虑更广泛的社会负担。
与其他非典型抗精神病药物相比，AOM 400在慢性稳定型精神分裂症的维持治疗中具有性价比；然而，鉴于PSA研究结果和相当的成本效益（即与RLAI相比），在开具抗精神病药物处方时，必须考虑各自治疗的产品特点和更广泛的益处。
未来研究应评估在精神分裂症病程早期使用LAI抗精神病药物，以确定精神病发作后不久改善依从性和治疗效果是否有可能改变疾病轨迹。此外，应评估疾病轨迹的变化是否可以减轻国家医疗服务体系的成本和资源压力。
