TY - JOUR

T1 - Identifying clinically relevant agranulocytosis in people registered on the UK clozapine Central Non-Rechallenge Database: retrospective cohort study

AU - Oloyede, Ebenezer

AU - Bachmann, Christian J

AU - Dzahini, Olubanke

AU - Lopez Alcaraz, Juan Miguel

AU - Singh, Shaurya Dev

AU - Vallianatu, Kalliopi

AU - Funk, Burkhardt

AU - Whiskey, Eromona

AU - Taylor, David

N1 - Publisher Copyright: Copyright © The Author(s), 2024.

PY - 2024/11

Y1 - 2024/11

N2 - Background Clozapine is the most effective antipsychotic for treatment-resistant psychosis. However, clozapine is underutilised in part because of potential agranulocytosis. Accumulating evidence indicates that below-threshold haematological readings in isolation are not diagnostic of life-threatening clozapine-induced agranulocytosis (CIA). Aims To examine the prevalence and timing of CIA using different diagnostic criteria and to explore demographic differences of CIA in patients registered on the UK Central Non-Rechallenge Database (CNRD). Method We analysed data of all patients registered on the UK Clozaril® Patient Monitoring Service Central Non-Rechallenge Database (at least one absolute neutrophil count (ANC) < 1.5 × 109/L and/or white blood cell count < 3.0 × 109/L) between May 2000 and February 2021. We calculated prevalence rates of agranulocytosis using threshold-based and pattern-based criteria, stratified by demographic factors (gender, age and ethnicity). Differences in epidemiology based on rechallenge status and clozapine indication were explored. The proportion of patients who recorded agranulocytosis from a normal ANC was explored. Results Of the 3029 patients registered on the CNRD with 283 726 blood measurements, 593 (19.6%) were determined to have threshold-based agranulocytosis and 348 (11.4%) pattern-based agranulocytosis. In the total sample (75 533), the prevalence of threshold-based agranulocytosis and pattern-based agranulocytosis was 0.8% and 0.5%, respectively. The median time to threshold-based agranulocytosis was 32 weeks (IQR 184) and 15 (IQR 170) weeks for pattern-based agranulocytosis. Among age groups, the prevalence of pattern-based agranulocytosis and threshold-based agranulocytosis was highest in the >48 age group. Prevalence rates were greatest for White (18%) and male individuals (13%), and lowest for Black individuals (0.1%). The proportion of people who were determined to have pattern-based agranulocytosis without passing through neutropenia was 70%. Conclusions Threshold-based definition of agranulocytosis may over-diagnose CIA. Monitoring schemes should take into consideration neutrophil patterns to correctly identify clinically relevant CIA. In marked contrast to previous studies, CIA occurred least in Black individuals and most in White individuals.

AB - Background Clozapine is the most effective antipsychotic for treatment-resistant psychosis. However, clozapine is underutilised in part because of potential agranulocytosis. Accumulating evidence indicates that below-threshold haematological readings in isolation are not diagnostic of life-threatening clozapine-induced agranulocytosis (CIA). Aims To examine the prevalence and timing of CIA using different diagnostic criteria and to explore demographic differences of CIA in patients registered on the UK Central Non-Rechallenge Database (CNRD). Method We analysed data of all patients registered on the UK Clozaril® Patient Monitoring Service Central Non-Rechallenge Database (at least one absolute neutrophil count (ANC) < 1.5 × 109/L and/or white blood cell count < 3.0 × 109/L) between May 2000 and February 2021. We calculated prevalence rates of agranulocytosis using threshold-based and pattern-based criteria, stratified by demographic factors (gender, age and ethnicity). Differences in epidemiology based on rechallenge status and clozapine indication were explored. The proportion of patients who recorded agranulocytosis from a normal ANC was explored. Results Of the 3029 patients registered on the CNRD with 283 726 blood measurements, 593 (19.6%) were determined to have threshold-based agranulocytosis and 348 (11.4%) pattern-based agranulocytosis. In the total sample (75 533), the prevalence of threshold-based agranulocytosis and pattern-based agranulocytosis was 0.8% and 0.5%, respectively. The median time to threshold-based agranulocytosis was 32 weeks (IQR 184) and 15 (IQR 170) weeks for pattern-based agranulocytosis. Among age groups, the prevalence of pattern-based agranulocytosis and threshold-based agranulocytosis was highest in the >48 age group. Prevalence rates were greatest for White (18%) and male individuals (13%), and lowest for Black individuals (0.1%). The proportion of people who were determined to have pattern-based agranulocytosis without passing through neutropenia was 70%. Conclusions Threshold-based definition of agranulocytosis may over-diagnose CIA. Monitoring schemes should take into consideration neutrophil patterns to correctly identify clinically relevant CIA. In marked contrast to previous studies, CIA occurred least in Black individuals and most in White individuals.

KW - Informatics

KW - Psychotic disorders

KW - antipsychotics

KW - Business informatics

UR - http://www.scopus.com/inward/record.url?scp=85201932211&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/63d9c897-6779-374d-8299-6f0b84e35587/

U2 - 10.1192/bjp.2024.104

DO - 10.1192/bjp.2024.104

M3 - Journal articles

C2 - 39149780

VL - 225

SP - 484

EP - 491

JO - The British Journal of Psychiatry

JF - The British Journal of Psychiatry

SN - 0007-1250

IS - 5

ER -