Cost effectiveness of pharmacogenetic-guided clozapine administration based on risk of HLA variants in Japan and the UK

kohei Ninomiya, Takeo Saito, Tomo Okochi, Satoru Taniguchi, Ayu Shimasaki, Rei Aoki, Takeo Hata, Taisei Mushiroda, Tetsufumi Kanazawa, Masashi Ikeda, Nakao Iwata

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Pharmacogenetics/pharmacogenomics have enabled the detection of risk of human leukocyte antigen (HLA) variants for clozapine-induced agranulocytosis/granulocytopenia (CIAG). To apply this evidence to the clinical setting, we compared the cost-effectiveness of the proposed “HLA-guided treatment schedule” and the “current schedule” being used in Japan and the United Kingdom (UK) (absolute neutrophil count (ANC) cutoff at 1500/mm3); in the “HLA-guided treatment schedules,” we considered a situation wherein the HLA test performed before clozapine initiation could provide “a priori information” by detecting patients harboring risk of HLA variants (HLA-B*59:01 and “HLA-B 158T/HLA-DQB1 126Q” for Japanese and Caucasian populations, respectively), a part of whom can then avoid CIAG onset (assumed 30% “prevention rate”). For the primary analysis, we estimated the incremental cost-effectiveness ratio (ICER) of “HLA-guided treatment schedule” and “current schedule” used in Japan and the UK, using a Markov model to calculate the cost and quality-adjusted life years (QALYs) over a 10-year time period. Furthermore, as an explorative analysis, we simulated several situations with various ANC cutoffs (1000/mm3 and 500/mm3) and plotted the cost/QALYs for each option to identify the best, or estimate the next best candidate option applicable in actual clinical settings. The primary probabilistic analysis showed that the “HLA-guided treatment schedule” was more cost effective than the “current schedule”; the ICER was £20,995 and £21,373 for the Japanese and the UK populations, respectively. Additional simulation revealed that the treatment option of ANC cutoff at 500/mm3 without HLA screening was the most cost-effective option; however, several options may be candidates to break away from the “current schedule” of ANC cutoff at 1500/mm3. Owing to its cost-effectiveness, we propose such pharmacogenetic-guided/pharmacogenomic-guided clozapine treatment for use in the real-world setting, which provides key information for optimization of clinical guidelines for high-risk patients for gradual change of clozapine treatment schedule under the safety consideration.

Original languageEnglish
Article number362
JournalTranslational psychiatry
Issue number1
Publication statusPublished - 06-2021

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry


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