The Safety of 12-Weekly Monitoring of Neutrophil Count in Long-Term Clozapine Patients

长期服用氯氮平患者每12周监测一次中性粒细胞计数的安全性

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Abstract

INTRODUCTION: Clozapine is the only truly effective treatment for refractory schizophrenia, but its use is constrained by the requirements for frequent monitoring of neutrophil counts. In the UK during the COVID-19 pandemic, the frequency of clozapine blood monitoring was reduced in some units from 4-weekly to 12-weekly. We aimed to investigate the outcomes of reduced monitoring in long-term clozapine patients. METHODS: This was an anonymous, retrospective, observational cohort study. No restrictions were applied regarding care setting (i.e., outpatients or inpatients). All patients who registered for reduced frequency haematological monitoring from 1 March 2020 to 1 November 2022 were included and followed up till 1 August 2024. The primary outcome was death resulting from clozapine-induced agranulocytosis (CIA). Secondary outcomes were the proportion of patients with mild to moderate neutropenia during the follow-up period and the proportion of patients who reverted to standard monitoring during the study period. RESULTS: Amongst 1025 patients, there were no cases of agranulocytosis over 3365.9 patient-years of 12-weekly blood monitoring (incident rate 0.0 per 100 person-years). There were 43 episodes of mild neutropenia (so-called amber results-1.5-2.0 × 10(9)/L) or neutropenia (red results < 1.5 × 10(9)/L), an overall incident rate of 1.28 per 100 person-years. During follow-up, 41 patients (4%) reverted permanently to standard 4-weekly monitoring, and 157 patients (15%) temporarily interrupted reduced frequency monitoring but restarted 12-weekly monitoring before the end of the follow-up period. In total, 42 patients (4%) died during the observation period-no death was related to agranulocytosis. CONCLUSION: Reducing the frequency of clozapine haematological monitoring to 12-weekly was safe in a group of long-term patients. No cases of agranulocytosis occurred and no deaths due to agranulocytosis were recorded. Most patients remained on extended-interval monitoring.

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