Background

Despite worldwide use of parenteral methotrexate (pMTX), health economic evidence for its use in Crohn’s disease (CD) is limited. The low price of this generic drug has removed any commercial incentive to further invest in research. However, there is an unmet need for treatment of mild-to-moderate CD, since biological/targeted therapies are usually reserved for patients with more severe disease due to the higher costs of these treatments.

Objective

To evaluate the cost-effectiveness of pMTX compared to the standard of care (SOC, i.e., high doses of oral corticosteroids (hdCS) followed by gradual tapering) for the treatment of mild-to-moderate CD in the Czech Republic.

Methods

We developed a 3-year Markov model with a 1-week cycle length comprising five health states. The model projected quality-adjusted life-years (QALYs) and costs from the healthcare payers’ perspective. Efficacy data were obtained from a systematic literature review of clinical trials and extrapolated using survival analysis.

Results

Over a 3-year time-horizon, pMTX yields additional 0.111 QALYs (1.798 vs. 1.687) at an additional cost of €513 (€3087 vs. €2574), with an incremental deterministic (probabilistic) cost-effectiveness ratio of €4627 (€4742)/QALY, far below the willingness-to-pay (WTP) threshold (≈ €47,000/QALY). The probabilistic sensitivity analysis showed that the probability of pMTX being cost-effective was 100%. A one-way sensitivity and scenario analysis confirmed the robustness of the base-case result.

Conclusion

Parenteral MTX proved to be cost-effective in patients with mild-to-moderate CD. This is the first published cost-effectiveness analysis of pMTX for this indication. It also shows an example of a lack of valuation of generic therapy despite its cost-effectiveness and a clear benefit to the healthcare system.

中文翻译：

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肠外甲氨蝶呤治疗克罗恩病的成本-效果分析

背景

尽管在全球范围内使用肠外甲氨蝶呤 (pMTX)，但其用于治疗克罗恩病 (CD) 的健康经济证据有限。这种仿制药的低价消除了进一步投资于研究的任何商业动机。然而，治疗轻度至中度 CD 的需求尚未得到满足，因为生物/靶向治疗通常只用于病情较严重的患者，因为这些治疗的成本较高。

客观的

评估 pMTX 与护理标准（SOC，即高剂量口服皮质类固醇 (hdCS) 然后逐渐减量）相比在捷克共和国治疗轻度至中度 CD 的成本效益。

方法

我们开发了一个 3 年马尔可夫模型，周期长度为 1 周，包括五种健康状态。该模型从医疗保健支付者的角度预测了质量调整生命年 (QALY) 和成本。疗效数据来自临床试验的系统文献综述，并使用生存分析进行推断。

结果

在 3 年的时间范围内，pMTX 产生额外的 0.111 QALY（1.798 对 1.687），额外成本为 513 欧元（3087 欧元对 2574 欧元），增量确定性（概率）成本效益比为 4627 欧元(€4742)/QALY，远低于支付意愿 (WTP) 阈值（≈ €47,000/QALY）。概率敏感性分析表明，pMTX 具有成本效益的概率为 100%。单向敏感性和情景分析证实了基本案例结果的稳健性。

结论

肠外 MTX 被证明对轻度至中度 CD 患者具有成本效益。这是针对该适应症首次发布的 pMTX 成本效益分析。它还显示了一个例子，尽管仿制药具有成本效益并且对医疗保健系统有明显的好处，但它仍然缺乏估值。