Clozapine and neutrophil response in patients of African descent: A six-month, multinational, prospective, open-label clinical trial.
Publication/Presentation Date
6-1-2024
Abstract
INTRODUCTION: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it is markedly underutilized, particularly in the US Black population, partly because of concern over clozapine-associated low absolute neutrophil count (ANC). People of African descent have a lower normative ANC range than the White population, which is associated with a specific "ACKR1-null" ("Duffy null") CC genotype (SNP rs2814778) on the ACKR1 gene, termed benign ethnic neutropenia (BEN). The range of ANC variability and safety of clozapine have not been established in people with BEN or examined prospectively in people of African descent.
METHODS: We completed a multisite, 6-month, prospective, open-label clinical trial of clozapine treatment in people of African descent with schizophrenia spectrum disorders for whom clozapine was clinically indicated, with or without the ACKR1-null genotype. We examined clozapine safety and weekly ANC during clozapine treatment and evaluated ANC variability by ACKR1-null genotype, sex, study site, and clozapine dosing using repeated measures analysis of covariance. Genotype was assayed using TaqMan® technology.
RESULTS: We enrolled 274 participants, of whom 227 (82.8 %) completed 6 months of clozapine treatment. There was one case of severe neutropenia (< 500 cells/mm
CONCLUSION: To our knowledge, this is the largest prospective clozapine trial in people of African descent. Severe neutropenia was rare, despite the high prevalence (80 %) of the ACKR1-null genotype. Our findings suggest that clozapine can be used safely in Black patients including those with BEN.
Volume
268
First Page
312
Last Page
322
ISSN
1573-2509
Published In/Presented At
Kelly, D. L., Glassman, M., Wonodi, I., Vyas, G., Richardson, C. M., Nwulia, E., Wehring, H. J., Oduguwa, T., Mackowick, M., Hipolito, M. M. S., Peters, O., Rai, N., Park, J., Adebayo, A. O., Gorelick, D. A., Weiner, E., Liu, F., Kearns, A. M., Adams, H. A., Love, R. C., … Adebayo, R. (2024). Clozapine and neutrophil response in patients of African descent: A six-month, multinational, prospective, open-label clinical trial. Schizophrenia research, 268, 312–322. https://doi.org/10.1016/j.schres.2023.08.002
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
37633776
Department(s)
Administration and Leadership
Document Type
Article