Alexion Pharmaceuticals, Inc., Boston, MA, USA.
Broadstreet Health Economics and Outcomes Research, Vancouver, Canada.
Hematology. 2020 Dec;25(1):327-334. doi: 10.1080/16078454.2020.1807226.
Although complement inhibition is highly effective, patients with paroxysmal nocturnal hemoglobinuria (PNH) may experience intravascular breakthrough hemolysis (BTH). Underlying causes may include elevated free C5, pregnancy, or non-pregnancy complement-activating conditions (e.g. infections). This study compared BTH-related resource utilization and costs in PNH patients treated with eculizumab versus ravulizumab. A cost model was developed using data from a targeted literature review and a survey of experienced clinicians. Costs associated with BTH episodes were calculated by cause and weighted by the proportion attributed to each cause and the cost of treating each episode. The model captured direct medical costs in 2018 US dollars. Annual BTH-related healthcare resource utilization was also calculated. BTH episodes in the literature were commonly associated with elevated lactate dehydrogenase and aspartate aminotransferase, hemoglobinuria, transfusion needs, and/or recurrence of PNH symptoms. The majority of BTH management costs in eculizumab-treated patients related to changing from the approved dosing regimen following an episode of BTH, rather than acute management. No ongoing dosing changes were expected for ravulizumab-treated patients following episodes of BTH, substantially reducing its ongoing management costs. Resource utilization was greater for eculizumab-treated patients than ravulizumab-treated patients due to higher incidence of BTH, and risk of elevated free C5-related BTH. Total incremental cost was substantially lower for ravulizumab- vs eculizumab-treated patients ($407 vs $9379); results were consistent when pregnant women were not included ($386 vs $3472). Overall resource use and costs for BTH are estimated to be lower for PNH patients receiving ravulizumab compared with eculizumab.
尽管补体抑制作用非常有效，但阵发性夜间血红蛋白尿症（PNH）患者可能会经历血管内突破性溶血（BTH）。潜在的原因可能包括 C5 游离升高、妊娠或非妊娠补体激活状态（例如感染）。本研究比较了依库珠单抗和拉维珠单抗治疗 PNH 患者的 BTH 相关资源利用和成本。使用靶向文献综述和经验丰富的临床医生调查的数据开发了成本模型。通过病因计算与 BTH 发作相关的成本，并根据每种病因的比例和治疗每个发作的成本进行加权。该模型以 2018 年美元捕获直接医疗成本。还计算了年度与 BTH 相关的医疗保健资源利用情况。文献中的 BTH 发作通常与乳酸脱氢酶和天冬氨酸转氨酶升高、血红蛋白尿、输血需求和/或 PNH 症状复发有关。依库珠单抗治疗患者的大多数 BTH 管理成本与 BTH 发作后改变批准剂量方案有关，而不是急性管理。拉维珠单抗治疗患者在 BTH 发作后预计不会进行持续剂量调整，从而大大降低了其持续管理成本。由于 BTH 发生率较高以及与 C5 游离升高相关的 BTH 风险，依库珠单抗治疗患者的资源利用情况大于拉维珠单抗治疗患者。拉维珠单抗与依库珠单抗治疗患者的增量总成本显著降低（407 美元 vs 9379 美元）；当不包括孕妇时，结果是一致的（386 美元 vs 3472 美元）。与依库珠单抗相比，接受拉维珠单抗治疗的 PNH 患者的总体 BTH 资源使用和成本估计较低。
