{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:29:18Z","timestamp":1780453758633,"version":"3.54.1"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>The identification of pharmacogenetic factors that increase the susceptibility to clozapine-induced agranulocytosis or granulocytopenia (CIAG) has received increasing interest. The SLCO1B3-SCLO1B7 variant (rs149104283) and single amino acid changes in human leukocyte antigen (HLA) HLA-DQB1 (126Q) and HLA-B (158T) were associated with an increased risk of CIAG. In this study, we evaluated the effectiveness and cost-effectiveness of adding the SLCO1B3-SCLO1B7 to HLA variants as a new pharmacogenomic (PGx) approach and explored the evolution of a cohort of schizophrenic patients taking long-term clozapine as a third-line antipsychotic medication. The decision model included probabilistic and deterministic sensitivity analyses to assess the expected costs and quality-adjusted life-years (QALYs). The current monitoring scheme was compared with the PGx-guided strategy, where all patients underwent pre-emptively a genetic test before taking clozapine, over 10 years. By adding the SLCO1B3-SCLO1B7 variant into HLA variants, CIAG sensitivity increased from 36.0% to 43.0%, the specificity decreased from 89.0% to 86.9%, and the probability of cost-effectiveness improved from 74.1% to 87.8%. The incremental cost-effectiveness ratio was \u00a316,215 per QALY and remained below the conventional decision threshold (\u00a330,000 or US$50,000 per QALY). Therefore, the SLCO1B3-SCLO1B7 variant, as an additional risk allele to HLA variants, increases preemptive test sensitivity and improves the effectiveness and cost-effectiveness of PGx-guided clozapine administration.<\/jats:p>","DOI":"10.3389\/fphar.2022.1016669","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T08:01:48Z","timestamp":1665734508000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacogenomic-guided clozapine administration based on HLA-DQB1, HLA-B and SLCO1B3-SLCO1B7 variants: an effectiveness and cost-effectiveness analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Kohei","family":"Ninomiya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nakao","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois R.","family":"Girardin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1056\/NEJM199307153290303","article-title":"Clozapine-induced agranulocytosis. 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