Optimizing outcomes in clozapine rechallenge following neutropenia using human leukocyte antigen typing: A case report

Yamaki, Naruhisa; Hishimoto, Akitoyo; Otsuka, Ikuo; Sasada, Toru; Boku, Shuken; Takeo, Satoshi; Yasuda, Yuka; Yamamori, Hidenaga; Ikeda, Masashi; Ikeda, Manabu; Sora, Ichiro; Iwata, Nakao; Hashimoto, Ryota

doi:10.1111/pcn.12505

Cited by 8 publications

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“…Conversely, we examined the diagnostic performance of non-risk allele (alleles except for HLA-B * 59:01 ) on non-CIA among CIG patients and demonstrated a moderate, positive predictive value for detecting non-CIA subjects in the CIG group without the risk allele, suggesting a potential candidate for re-challenging with clozapine treatment in a Japanese population (Saito et al, 2016 ). Based on this finding, a re-challenging with clozapine following neutropenia in a patient with a low risk of CIAG ( HLA-B * 52:01/52:01 ) was successfully conducted (Yamaki et al, 2017 ). The decision regarding clozapine re-challenge or withdrawal in case of CIAG should be based on careful consideration of risk factors, which can be facilitated by genetic testing in the future (Wicinski and Weclewicz, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Clozapine Pharmacogenetic Studies in Schizophrenia: Efficacy and Agranulocytosis

et al. 2018

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Clozapine is an efficacious atypical antipsychotic for treatment-refractory schizophrenia. Clinical response and appearance of adverse events vary among individual patients receiving clozapine, with genetic and non-genetic factors potentially contributing to individual variabilities. Pharmacogenetic studies investigate associations between genetic variants and drug efficacy and toxicity. To date, most pharmacogenetic studies of clozapine have been conducted through candidate gene approaches. A recent advance in technology made it possible to perform comprehensive genetic mapping underlying clinical phenotypes and outcomes, which allow novel findings beyond biological hypotheses based on current knowledge. In this paper, we will summarize the studies on clozapine pharmacogenetics that have extensively examined clinical response and agranulocytosis. While there is still limited evidence on clozapine efficacy, recent genome-wide studies provide further evidence of the involvement of the human leukocyte antigen (HLA) region in clozapine-induced agranulocytosis.

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Section: Discussionmentioning

confidence: 99%

Clozapine Pharmacogenetic Studies in Schizophrenia: Efficacy and Agranulocytosis

et al. 2018

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“…A recent study showed that human leukocyte antigen (HLA)‐B*59:01 was a risk factor for clozapine‐induced agranulocytosis/granulocytopenia in the Japanese population (Saito et al, ). Although clozapine‐induced agranulocytosis is rarely observed, the prior risk assessments, such as HLA typing and/or careful monitoring of blood cell counts, are needed for the safe use of clozapine (Yamaki et al, ). Guest, Sokoluk, MacCrimmon, and Uetrecht () also suggested that the time course of clozapine toxicity on human neutrophils was related to multiple factors such as clozapine metabolites, anticlozapine antibodies, and antigen‐specific T cells, whereas the precise molecular mechanisms are still unknown.…”

Section: Discussionmentioning

confidence: 99%