背景:氯氮平在难治性精神分裂症中具有独特的功效,并且已知会引起免疫副作用。中性粒细胞的短暂峰值通常发生在氯氮平治疗的第一周。关于氯氮平的中性粒细胞变化是否与治疗反应有关,文献中有矛盾的证据。
目的:本研究旨在进一步检查中性粒细胞对氯氮平反应的变化,并探讨中性粒细胞轨迹与治疗反应之间的关联。
方法:一项对首次使用氯氮平治疗并持续至少2年的患者进行的回顾性队列研究确定了425例患者(69%为男性/31%为女性)。基线时的中性粒细胞计数,主要通过与氯氮平监测服务的数据联系获得3周和1个月。临床总体印象-严重性(CGI-S)在开始氯氮平时和在2年时从病例记录中评估。进行潜在类别生长分析(LCGA)以定义治疗第一个月期间中性粒细胞变化的不同轨迹。然后进行逻辑回归以研究1个月中性粒细胞计数变化的轨迹与2年时的临床反应之间以及基线中性粒细胞计数与反应之间的关联。
结果:在原始队列中,397(93%)患者在氯氮平治疗的前6周内有可用的中性粒细胞数据。LCGA揭示了中性粒细胞轨迹的显着差异,其中三类模型是最简约的。这些类别具有相似的轨迹曲线,但主要在总体中性粒细胞计数上有所不同:低,高正常和高中性粒细胞类,包括52%,40%和8%的样品分别。高正常组的成员与对氯氮平的阳性反应的几率显着增加有关,与低中性粒细胞组相比[比值比(OR)=2.10,p值=0.002;95%置信区间(95%CI)=1.31-3.36].基线中性粒细胞计数是2年时对氯氮平反应的预测因子,≥5×109/l的计数与阳性反应显着相关(OR=1.60,p值=0.03;95%CI=1.03-2.49)。
结论:我们的数据与低水平炎症患者的假设一致,反映在正常中性粒细胞计数较高,更有可能对氯氮平产生反应,提高了氯氮平通过免疫机制发挥其优异疗效的可能性。
Clozapine has unique effectiveness in treatment-resistant schizophrenia and is known to cause immunological side-effects. A transient spike in neutrophils commonly occurs in the first weeks of clozapine therapy. There is contradictory evidence in the literature as to whether neutrophil changes with clozapine are linked to treatment response.
The current study aims to further examine the neutrophil changes in response to clozapine and explore any association between neutrophil trajectory and treatment response.
A retrospective cohort study of patients undergoing their first treatment with clozapine and continuing for at least 2 years identified 425 patients (69% male/31% female). Neutrophil counts at baseline, 3 weeks and 1 month were obtained predominantly by linkage with data from the clozapine monitoring service. Clinical Global Impression- Severity (CGI-S) was rated from case notes at the time of clozapine initiation and at 2 years. Latent class growth analysis (LCGA) was performed to define distinct trajectories of neutrophil changes during the first month of treatment. Logistic regression was then conducted to investigate for association between the trajectory of neutrophil count changes in month 1 and clinical response at 2 years as well as between baseline neutrophil count and response.
Of the original cohort, 397 (93%) patients had useable neutrophil data during the first 6 weeks of clozapine treatment. LCGA revealed significant differences in neutrophil trajectories with a three-class model being the most parsimonious. The classes had similar trajectory profiles but differed primarily on overall neutrophil count: with low, high-normal and high neutrophil classes, comprising 52%, 40% and 8% of the sample respectively. Membership of the high-normal group was associated with significantly increased odds of a positive response to clozapine, as compared to the low neutrophil group [Odds ratio (OR) = 2.10, p-value = 0.002; 95% confidence interval (95% CI) = 1.31-3.36]. Baseline neutrophil count was a predictor of response to clozapine at 2 years, with counts of ≥5 × 109/l significantly associated with positive response (OR = 1.60, p-value = 0.03; 95% CI = 1.03-2.49).
Our data are consistent with the hypothesis that patients with low-level inflammation, reflected in a high-normal neutrophil count, are more likely to respond to clozapine, raising the possibility that clozapine exerts its superior efficacy via immune mechanisms.