Precision Medicine Center of Excellence in Schizoaffective Disorders, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Precision Medicine Center of Excellence in Schizoaffective Disorders, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Schizophr Res. 2024 Oct;272:104-109. doi: 10.1016/j.schres.2024.08.018. Epub 2024 Aug 29.
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.
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.
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]).
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.
对氯氮平相关中性粒细胞减少症的担忧导致氯氮平的利用率低，且在获得途径方面存在种族差异。具有非洲血统的人更有可能出现正常绝对中性粒细胞计数（ANC）较低的情况，这与达菲无效基因多态性有关。美国最近缺乏氯氮平相关中性粒细胞减少症的数据。
在 2013 年至 2023 年间，在约翰霍普金斯医学电子病历（EMR）中确定了接受氯氮平治疗的患者。如果在开始氯氮平之前有两次 ANC<2000 个细胞/μL，且相隔>30 天，则分配达菲无效相关中性粒细胞计数（DANC）。探讨了中性粒细胞减少症的发生率、首次中性粒细胞减少症的时间和人口统计学差异。
974 名患者接受了氯氮平治疗，并且有 ANC 可用，其中 63.9%为男性，51.1%为白人，39%为黑人。287 名患者被认为在研究期间开始接受氯氮平治疗，其中 62.4%为男性，46%为白人，44.9%为黑人。没有患者发生严重中性粒细胞减少症。59（6.1%）名患者发生轻度或中度中性粒细胞减少症。19（6.6%）名新开始接受氯氮平治疗的患者被认为有 DANC，并且没有人发生中性粒细胞减少症。在 16 名新开始接受氯氮平治疗且发生中性粒细胞减少症的患者中，有 11 名在 8 个月内发生。在新开始接受氯氮平治疗的患者中，没有发现组间的人口统计学差异。对于非新开始接受氯氮平治疗的患者，由于无法进行 DANC 分配，黑人患者比白人患者更有可能发生中性粒细胞减少症（OR 3.48，95%CI [1.65，7.73]）。
据我们所知，这是过去十年中在美国进行的第一项关于氯氮平相关中性粒细胞减少症的观察性研究，其中包括相当比例的黑人患者。ANC 监测要求可能过于严格，导致氯氮平的利用率低。
