Lancet Psychiatry

ANC monitoring in patients on clozapine: Can it be safely stopped at any point?

December 6, 2023

According to a large retrospective analysis, most cases of serious neutropenia leading to clozapine cessation occur within 18 weeks of treatment initiation and become negligible after 2 years. Thus, weekly hematological monitoring after the first 18 weeks could be safely reduced to q4wks and ceased after 2 years unless clinically indicated.

• Researchers performed a retrospective analysis of the Australian and New Zealand Viatris Pharmacovigilance system between June 1990 and Oct 2022. Patients were excluded if they started clozapine before 1990, didn’t have a hematology test within 2 weeks of start date, or had no follow-up. Investigators documented minor neutropenia (absolute neutrophil count [ANC] 1.0-1.5 × 10^9 per L) and serious neutropenia (ANC <1.0 × 10^9 per L) leading to cessation of clozapine within 6 weeks of the neutropenic event.
• A total of 26,630 individuals (66% male; mean age, 36.1 years) with 2.6 million ANC values were included in the analysis. 1,146 patients (4.3%) had minor neutropenia, 313 (1.2%) had serious neutropenia leading to cessation, and 223 (0.8%) had serious neutropenia unrelated to clozapine without cessation.
• In those with no previous clozapine exposure (n=15,973), the cumulative incidence of serious neutropenia leading to cessation was 0.9% at 18 weeks and 1.4% at 2 years; the weekly incidence rate for serious neutropenia leading to cessation peaked at 9 weeks (0.128%) and fell to a rolling average weekly incidence of 0.001% by 2 years.
• For minor neutropenia, the cumulative incidence was 1.7% at 18 weeks and 3.5% at 2 years; the weekly incidence rate peaked at 9 weeks (0.218%) and fell to a stable rolling average of 0.01%. Median time to a serious neutropenic event leading to cessation was 17 weeks. Previous clozapine exposure reduced the risk of serious neutropenia leading to cessation (odds ratio, 0.19; 95% confidence interval, 0.12-0.31; p <0·0001).

Source:

Northwood K, et al. (2023, November 28). Lancet Psychiatry. Evaluating the epidemiology of clozapine-associated neutropenia among people on clozapine across Australia and Aotearoa New Zealand: a retrospective cohort study. https://pubmed.ncbi.nlm.nih.gov/38040009/