Westerhout Kirsten Y, Bouwmeester Walter, Duchesne Inge, Pisini Marta, Piena Marjanne A, Damele Francesco, Gueron Beatrice, Treur Maarten, Belsey Jonathan
Pharmerit BV, Marten Meesweg, Rotterdam, the Netherlands.
Janssen EMEA, Turnhoutseweg, Beerse, Belgium.
Clinicoecon Outcomes Res. 2017 Feb 27;9:163-172. doi: 10.2147/CEOR.S117650. eCollection 2017.
Patients with genotype-1 hepatitis C virus infection who have failed to respond to standard therapy or who relapse following treatment may be considered for an interferon-free regimen incorporating a nonstructural protein 5A (NS5A) inhibitor. Sustained virologic response (SVR) with these regimens is typically >90%, but this is reduced in patients with NS5A resistance. European Association for Study of the Liver guidelines recommend simeprevir + sofosbuvir ± ribavirin (SMV+SOF±R) for re-treating patients failing an NS5A inhibitor-containing regimen. An alternative strategy would be to test for NS5A resistance prior to treatment, with therapy optimized based on the results. This study investigates the cost-effectiveness of this strategy.
A Markov model was used to estimate disease progression for treatment-experienced genotype 1 patients with severe fibrosis or compensated cirrhosis. Targeted treatment with either SMV+SOF±R or sofosbuvir + ledipasvir ± ribavirin (SOF+LDV±R) based on pretreatment NS5A resistance testing was compared to routine SOF+LDV±R without testing. Treatment duration was 12 or 24 weeks for patients with severe fibrosis or compensated cirrhosis (Metavir F3/F4). SVR data for the treatment options were based on the results of published clinical trials. The analysis was carried out from the perspective of the Italian National Health Service.
Optimized treatment using NS5A resistance testing yielded 0.163 additional QALYs and increased costs of €2,789 per patient versus no testing. The incremental cost-effectiveness ratio (ICER) was €17,078/QALY. Sensitivity analysis identified the SVR attributable to each of the treatment regimens as the most sensitive determinant of ICER (range: €10,055/QALY-€43,501/QALY across plausible range). Probabilistic sensitivity analysis demonstrated that, at a willingness-to-pay threshold of €30,000/QALY, the probability that NS5A-directed treatment will be cost-effective is 81.4%.
Optimizing therapy with either SMV+SOF±R or SOF+LDV±R based on pretreatment NS5A resistance testing was cost-effective from the perspective of the Italian National Health Service, in treatment-experienced patients with severe fibrosis or compensated cirrhosis.
基因型1丙型肝炎病毒感染患者若对标准治疗无反应或治疗后复发，可考虑采用含非结构蛋白5A（NS5A）抑制剂的无干扰素治疗方案。这些方案的持续病毒学应答（SVR）率通常>90%，但NS5A耐药患者的SVR率会降低。欧洲肝脏研究协会指南推荐使用simeprevir+索磷布韦±利巴韦林（SMV+SOF±R）对含NS5A抑制剂方案治疗失败的患者进行再治疗。另一种策略是在治疗前检测NS5A耐药情况，并根据检测结果优化治疗方案。本研究调查了该策略的成本效益。
采用马尔可夫模型估计有治疗经验的基因型1重度纤维化或代偿期肝硬化患者的疾病进展情况。将基于治疗前NS5A耐药检测结果采用SMV+SOF±R或索磷布韦+来迪派韦±利巴韦林（SOF+LDV±R）进行靶向治疗与不进行检测直接采用常规SOF+LDV±R治疗进行比较。重度纤维化或代偿期肝硬化（梅塔维分级F3/F4）患者的治疗疗程为12周或24周。各治疗方案的SVR数据基于已发表的临床试验结果。分析是从意大利国家卫生服务体系的角度进行的。
与不进行检测相比，采用NS5A耐药检测进行优化治疗，每位患者可多获得0.163个质量调整生命年（QALY），成本增加2789欧元。增量成本效益比（ICER）为17,078欧元/QALY。敏感性分析确定各治疗方案的SVR是ICER最敏感的决定因素（范围：在合理范围内为10,055欧元/QALY - 43,501欧元/QALY）。概率敏感性分析表明，在支付意愿阈值为30,000欧元/QALY时，基于NS5A检测的治疗具有成本效益的概率为81.4%。
从意大利国家卫生服务体系的角度来看，对于有治疗经验的重度纤维化或代偿期肝硬化患者，基于治疗前NS5A耐药检测结果采用SMV+SOF±R或SOF+LDV±R进行治疗优化具有成本效益。
