PMID- 34230449 OWN - NLM STAT- MEDLINE DCOM- 20210714 LR - 20210728 IS - 2158-3188 (Electronic) IS - 2158-3188 (Linking) VI - 11 IP - 1 DP - 2021 Jul 7 TI - Cost effectiveness of pharmacogenetic-guided clozapine administration based on risk of HLA variants in Japan and the UK. PG - 362 LID - 10.1038/s41398-021-01487-4 [doi] LID - 362 AB - 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/mm(3)); 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/mm(3) and 500/mm(3)) 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 pound20,995 and pound21,373 for the Japanese and the UK populations, respectively. Additional simulation revealed that the treatment option of ANC cutoff at 500/mm(3) 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/mm(3). 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. FAU - Ninomiya, Kohei AU - Ninomiya K AUID- ORCID: 0000-0001-6232-0008 AD - Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. FAU - Saito, Takeo AU - Saito T AD - Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. FAU - Okochi, Tomo AU - Okochi T AD - Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. FAU - Taniguchi, Satoru AU - Taniguchi S AD - Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. FAU - Shimasaki, Ayu AU - Shimasaki A AD - Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. FAU - Aoki, Rei AU - Aoki R AD - Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. FAU - Hata, Takeo AU - Hata T AD - Department of Pharmacy, Osaka Medical College Hospital, Takatsuki, Osaka, Japan. FAU - Mushiroda, Taisei AU - Mushiroda T AD - Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. FAU - Kanazawa, Tetsufumi AU - Kanazawa T AUID- ORCID: 0000-0003-3781-297X AD - Department of Neuropsychiatry, Osaka Medical College, Takatsuki, Osaka, Japan. FAU - Ikeda, Masashi AU - Ikeda M AUID- ORCID: 0000-0001-6237-2449 AD - Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. ikeda-ma@fujita-hu.ac.jp. FAU - Iwata, Nakao AU - Iwata N AUID- ORCID: 0000-0003-3189-6076 AD - Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. LA - eng GR - JP20dm0107097, JP20km0405208/Japan Agency for Medical Research and Development (AMED)/ GR - JP20dm0107097, JP20km0405201/Japan Agency for Medical Research and Development (AMED)/ GR - JP20km0405201/Japan Agency for Medical Research and Development (AMED)/ GR - JP20dm0107097, JP20km0405201/Japan Agency for Medical Research and Development (AMED)/ GR - JP26293266, JP17H04251/MEXT | Japan Society for the Promotion of Science (JSPS)/ GR - JP18K15497/MEXT | Japan Society for the Promotion of Science (JSPS)/ GR - JP25293253, JP16H05378/MEXT | Japan Society for the Promotion of Science (JSPS)/ GR - 20GC1017/Ministry of Health, Labour and Welfare (Ministry of Health, Labour and Welfare, Japan)/ GR - Private University Research Branding Project/Ministry of Education, Culture, Sports, Science and Technology (MEXT)/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210707 PL - United States TA - Transl Psychiatry JT - Translational psychiatry JID - 101562664 RN - 0 (HLA-B Antigens) RN - J60AR2IKIC (Clozapine) SB - IM MH - *Clozapine/adverse effects MH - Cost-Benefit Analysis MH - HLA-B Antigens MH - Humans MH - Japan MH - Pharmacogenetics MH - United Kingdom PMC - PMC8260588 COIS- Dr. N. Iwata has received research support or speakers' honoraria from, or has served as a consultant to Jansen, Glaxo SmithKline, Eli Lilly, Otsuka, Shionogi, Dainippon Sumitomo, Tanabe Mitsubishi, Daiichi-Sankyo. For the remaining authors none were declared. EDAT- 2021/07/08 06:00 MHDA- 2021/07/15 06:00 PMCR- 2021/07/07 CRDT- 2021/07/07 06:18 PHST- 2020/12/27 00:00 [received] PHST- 2021/06/10 00:00 [accepted] PHST- 2021/06/04 00:00 [revised] PHST- 2021/07/07 06:18 [entrez] PHST- 2021/07/08 06:00 [pubmed] PHST- 2021/07/15 06:00 [medline] PHST- 2021/07/07 00:00 [pmc-release] AID - 10.1038/s41398-021-01487-4 [pii] AID - 1487 [pii] AID - 10.1038/s41398-021-01487-4 [doi] PST - epublish SO - Transl Psychiatry. 2021 Jul 7;11(1):362. doi: 10.1038/s41398-021-01487-4.