BTK抑制药在B细胞淋巴瘤中的用药模式与治疗费用分析

Analysis of the utilization patterns and costs of BTK inhibitors in B-cell lymphoma

目的探究真实世界中布鲁顿酪氨酸激酶(BTK)抑制药的用药模式、治疗费用以及安全性。方法通过北京大学第三医院电子病历系统(EMR)构建BTK抑制药真实世界数据队列,并对患者的人口统计学特征与临床特征进行定性分析。通过计算用药频度(DDDs)与日均费用(DDDc),对BTK抑制药的药品用量与使用成本进行统计分析。此外,通过广义估计方程(GEE)对血小板聚集率相关影响因素进行探索性分析。结果共纳入193例患者,中位年龄65岁,女性77例(39.90%)。多数患者(n=109,56.48%)应用伊布替尼,77.20%患者同时联用化疗或靶向药物进行治疗。国家医保谈判政策的实施对伊布替尼和泽布替尼的临床治疗选择以及使用成本产生了较大影响。伊布替尼与泽布替尼DDDs差异从18.59倍降至1.41倍。伊布替尼的DDDc从1619.99元降至567.00元,而泽布替尼从706.25元降至340.00元,已低于伊布替尼。与伊布替尼相比,泽布替尼相关的治疗中断事件更少,其中血液系统毒性是导致治疗中断的主要药物不良事件(ADE)。此外,GEE模型表明,与未联合抗血小板药物相比,BTK抑制药联合抗血小板药物导致患者的血小板聚集率显著降低[β=-34.35%,95%置信区间(CI):-41.60%~-27.11%,P<0.001];与泽布替尼治疗组相比,伊布替尼治疗组患者血小板聚集率显著降低(β=-12.38%,95%CI:-24.50%~-0.27%,P<0.05)。结论国家医保谈判政策实施后,临床对2种BTK抑制药的选择倾向性已无明显差异。与伊布替尼相比,泽布替尼在经济性、ADE导致的治疗中断以及对血小板聚集率的影响方面具有相对优势。

Objective To elucidate utilization patterns,cost and safety of Bruton's tyrosine kinase inhibitors(BTKi)in the real world.Methods A retrospective cohort was designed and constructed using real-world BTKi data from a single lymphoma center.Descriptive analysis was performed to describe the demographic and clinical characteristics of the population.Medicine utilization and cost were quantified by defined daily doses(DDDs)and defined daily dose cost(DDDc),respectively.A generalized estimating equation(GEE)was used to explore the potential influencing factors of platelet aggregation rate(PAR).Results The study cohort included 193 patients[median age,65 years;77(39.90%)women],most of whom received ibrutinib(n=109,56.48%),and 77.20%patients combined BTKi with chemotherapy or targeted therapy.TThe implementation of national negotiation policy had a large impact on medicine utilization and cost.The DDDs difference between the two BTKis was reduced from 18.55 to 1.41 times.The DDDc for ibrutinib decreased from 1619.99 Yuan to 567.00 Yuan,and that for zanubrutinib from 706.25 Yuan to 340.00 Yuan was already lower than ibrutinib.Interruptions were more readily observed in patients treated with ibrutinib,and hematological toxicity was the main adverse drug event(ADE)leading to treatment interruption.Besides,the GEE model showed that combining BTKi with antiplatelet medication significantly decreases the PAR[β=-34.35%,95%confidence interval(CI):-41.60%-27.11%,P<0.001].Compared to zanubrutinib,ibrutinib also notably reduces the PAR(β=-12.38%,95%CI:-24.50%-0.27%,P<0.05).Conclusion After the implementation of national negotiation policy,there is no significant dfference in the clinical preference for two BTKis.Compared with ibrutinib,zanubrutinib showed an advantage in terms of economic profile,treatment interruptions caused by ADE,and the effect on PAR.