Primary cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia caused by cold‐reactive antibodies that bind to red blood cells and lead to complement‐mediated hemolysis. Patients with primary CAD experience the burden of increased health resource utilization and reduced quality of life. The standard‐of‐care (SOC) in patients with primary CAD has included cold avoidance, transfusion support, and chemoimmunotherapy. The use of sutimlimab, a humanized monoclonal antibody that selectively inhibits C1‐mediated hemolysis, was shown to reduce transfusion‐dependence and improve quality of life across two pivotal phase 3 studies, further supported by 2‐year extension data. Using data from the transfusion‐dependent patient population that led to sutimlimab's initial FDA approval, we performed the first‐ever cost‐effectiveness analysis in primary CAD. The projected incremental cost‐effectiveness ratio (ICER) in our Markov model was $2 340 000/QALY, significantly above an upper‐end conventional US willingness‐to‐pay threshold of $150 000/QALY. These results are consistent across scenarios of higher body weight and a pan‐refractory SOC patient phenotype (i.e., treated sequentially with bendamustine‐rituximab, bortezomib, ibrutinib, and eculizumab). No parameter variations in deterministic sensitivity analyses changed our conclusion. In probabilistic sensitivity analysis, SOC was favored over sutimlimab in 100% of 10 000 iterations. Exploratory threshold analyses showed that significant price reduction (>80%) or time‐limited treatment (<18 months) followed by lifelong clinical remission off sutimlimab would allow sutimlimab to become cost‐effective. The impact of sutimlimab on health system costs with longer term follow‐up data merits future study and consideration through a distributional cost‐effectiveness framework.

中文翻译：

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舒替利单抗治疗冷凝集素病的成本效益

原发性冷凝集素病（CAD）是一种罕见的自身免疫性溶血性贫血，由冷反应性抗体与红细胞结合并导致补体介导的溶血引起。原发性 CAD 患者承受着卫生资源利用率增加和生活质量下降的负担。原发性 CAD 患者的标准护理 (SOC) 包括避免寒冷、输血支持和化学免疫治疗。两项关键的 3 期研究表明，使用 Sutimlimab（一种选择性抑制 C1 介导的溶血的人源化单克隆抗体）可以减少输血依赖性并改善生活质量，并得到 2 年扩展数据的进一步支持。利用导致 Sutimlimab 最初获得 FDA 批准的输血依赖患者群体的数据，我们对原发性 CAD 进行了首次成本效益分析。我们的马尔可夫模型中预计的增量成本效益比 (ICER) 为 2 340 000 美元/QALY，明显高于美国传统支付意愿上限 150 000 美元/QALY。这些结果在体重较高和泛难治性 SOC 患者表型（即依次使用苯达莫司汀-利妥昔单抗、硼替佐米、依鲁替尼和依库珠单抗治疗）的情况下是一致的。确定性敏感性分析中的参数变化没有改变我们的结论。在概率敏感性分析中，在 10000 次迭代中 100%，SOC 优于 Sutimlimab。探索性阈值分析表明，显着降价（>80%）或限时治疗（<18 个月），然后终身临床缓解 Sutimlimab 将使 Sutimlimab 变得具有成本效益。长期随访数据显示 Sutimlimab 对卫生系统成本的影响值得未来通过分配成本效益框架进行研究和考虑。