ACKR1/Duffy-null genotype testing for clozapine: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI-PGx).

Homozygous ACKR1 T>C variant (Duffy-null genotype): benign ethnic neutropenia interfering with clozapine hematological monitoring

Clozapine is the gold-standard treatment for refractory schizophrenia, but mandatory absolute neutrophil count (ANC) monitoring leads to unjustified exclusions in Duffy-null genotype carriers (ADAN), a benign ethnic neutropenia frequent in populations of African ancestry. The CERSI-PGx guideline recommends three ACKR1 genotyping eligibility criteria: pre-emptive testing for all new prescriptions, testing for patients in the non-rechallenge database, and reactive testing after below-threshold results. 129 Duffy-null patients could be identified in the first year, generating estimated savings of £42,732 to £727,990.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This guideline addresses a documented therapeutic inequity: patients of African ancestry are disproportionately excluded from clozapine due to non-pathological benign ethnic neutropenia. ACKR1 testing is a high cost-effectiveness PGx intervention that improves equitable access to the best available treatment for refractory schizophrenia. Adoption in UK practice could rapidly extend to other countries.

Analysis by Dr Thibaut Benquey