Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands,
Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Eur Addict Res. 2018;24(5):245-254. doi: 10.1159/000494127. Epub 2018 Nov 1.
Alcohol use disorders (AUD) are a major contributor to the global burden of disease, and have huge societal impact. Some studies show that AUD patients carrying the G-allele of the OPRM1 variant c.118A>G respond better to naltrexone, resulting in reduced relapse rates compared to carriers of the AA genotype. Genotype-guided treatment allocation of these patients carrying a G-allele to naltrexone could potentially improve the treatment outcome. However, cost-effectiveness of this strategy should be investigated before considering clinical implementation. We, therefore, evaluated costs and Quality-Adjusted Life-Years (QALYs), using a modelling approach, from an European perspective, of genotype-guided treatment allocation (G-allele carriers receiving naltrexone; AA homozygotes acamprosate or naltrexone) compared to standard care (random treatment allocation to acamprosate or naltrexone), by using a Markov model. Genotype-guided treatment allocation resulted in incremental costs of EUR 66 (95% CI -28 to 149) and incremental effects of 0.005 QALYs (95% CI 0.000-0.011) per patient (incremental cost-effectiveness ratio of EUR 13,350 per QALY). Sensitivity analyses showed that the risk ratio to relapse after treatment allocation had the largest impact on the cost-effectiveness. Depending on the willingness to pay for a gain of one QALY, probabilities that the intervention is cost-effective varies between 6 and 79%. In conclusion, pharmacogenetic treatment allocation of AUD patients to naltrexone, based on OPRM1 genotype, can be a cost-effective strategy, and could have potential individual and societal benefits. However, more evidence on the impact of genotype-guided treatment allocation on relapse is needed to substantiate these conclusions, as there is contradictory evidence about the effectiveness of OPRM1 genotyping.
酒精使用障碍（AUD）是全球疾病负担的主要原因，对社会有巨大影响。一些研究表明，携带 OPRM1 变体 c.118A>G 的 G 等位基因的 AUD 患者对纳曲酮的反应更好，与携带 AA 基因型的患者相比，复发率降低。对携带 G 等位基因的这些患者进行基于基因型的治疗分配，将其分配给纳曲酮，可能会改善治疗效果。然而，在考虑临床实施之前，应该调查这种策略的成本效益。因此，我们从欧洲的角度，使用建模方法，评估了基因型指导治疗分配（G 等位基因携带者接受纳曲酮；AA 纯合子接受阿坎酸或纳曲酮）与标准护理（随机分配接受阿坎酸或纳曲酮）相比的成本和质量调整生命年（QALYs），使用马尔可夫模型。基于基因型的治疗分配导致每位患者的增量成本为 66 欧元（95%CI-28 至 149），增量效应为 0.005 QALY（95%CI0.000 至 0.011），增量成本效益比为每 QALY13350 欧元。敏感性分析表明，治疗分配后复发的风险比对成本效益有最大影响。根据对获得一个 QALY 的支付意愿，该干预措施具有成本效益的概率在 6%至 79%之间。总之，基于 OPRM1 基因型对 AUD 患者进行纳曲酮的药物遗传学治疗分配可能是一种具有成本效益的策略，并可能具有潜在的个体和社会效益。然而，需要更多关于基于基因型的治疗分配对复发影响的证据来证实这些结论，因为关于 OPRM1 基因分型的有效性存在矛盾的证据。
