背景:对氯氮平相关性中性粒细胞减少症的担忧导致了氯氮平的利用不足和种族差异。有非洲血统的人更有可能有较低的标准绝对中性粒细胞计数(ANC),与Duffy空遗传多态性相关。美国缺乏氯氮平相关中性粒细胞减少症的最新数据。
方法:确定了2013年至2023年在约翰霍普金斯医学电子病历(EMR)中使用氯氮平的患者。如果有两个ANC<2000个细胞/μL,则分配Duffy空相关中性粒细胞计数(DANC),>相隔30天,在开始服用氯氮平之前.中性粒细胞减少症的发生率,第一次中性粒细胞减少症的时机,并探讨了人口统计学差异。
结果:974接受了氯氮平,并且有ANC\可用,男性占63.9%,51.1%白色,39%是黑人。在研究期间,推测有287人开始使用氯氮平,男性占62.4%,46%白色,和44.9%的黑人。没有患者出现严重的中性粒细胞减少症。59(6.1%)出现轻度或中度中性粒细胞减少症。19(6.6%)的新开始假定DANC,也没有出现中性粒细胞减少症.在16个假定的新起点中,有11个在八个月内发生了中性粒细胞减少症。对于假定的新开始,组间没有发现人口统计学差异。对于非新的开始,在DANC无法分配的地方,黑人患者比白人患者更容易发生中性粒细胞减少症(OR3.48,95%CI[1.65,7.73])。
结论:据我们所知,这是过去十年来美国首次对氯氮平相关中性粒细胞减少症进行的观察性研究,其中包括相当比例的黑人患者。ANC监控要求可能过于严格,导致氯氮平利用不足。
BACKGROUND: Concern about clozapine-associated neutropenia contributes to clozapine\'s underutilization and racial disparities in access. People with African ancestry are more likely to have lower normative absolute neutrophil counts (ANC), associated with the Duffy null genetic polymorphism. Recent data on clozapine-associated neutropenia in the US are lacking.
METHODS: Patients prescribed clozapine in the Johns Hopkins Medicine electronic medical record (EMR) between 2013 and 2023 were identified. Duffy null Associated Neutrophil Count (DANC) was assigned if there were two ANC\'s < 2000 cells/μL, >30 days apart, before starting clozapine. Rates of neutropenia, timing of first neutropenia, and demographic differences were explored.
RESULTS: 974 received clozapine and had ANC\'s available, with 63.9 % male, 51.1 % White, and 39 % Black. 287 were presumed to start clozapine during the study period, and were 62.4 % male, 46 % White, and 44.9 % Black. No patients developed severe neutropenia. 59 (6.1 %) developed mild or moderate neutropenia. 19 (6.6 %) new starts had presumed DANC, and none developed neutropenia. 11 of 16 presumed new starts who developed neutropenia did so within eight months. No demographic differences were found between groups for presumed new starts. For non-new starts, where DANC assignment was not possible, Black patients were more likely than White patients to develop neutropenia (OR 3.48, 95 % CI [1.65, 7.73]).
CONCLUSIONS: To our knowledge, this is the first observational study of clozapine-associated neutropenia in the US in the past decade, and it includes a substantial proportion of Black patients. ANC monitoring requirements may be too strict, contributing to clozapine underutilization.