Kakuta Yoichi, Kato Motohiro, Shimoyama Yusuke, Naito Takeo, Moroi Rintaro, Kuroha Masatake, Shiga Hisashi, Kinouchi Yoshitaka, Masamune Atsushi
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Pediatrics, University of Tokyo, Tokyo, Japan.
J Pharmacol Sci. 2023 Nov;153(3):161-169. doi: 10.1016/j.jphs.2023.09.002. Epub 2023 Sep 11.
The usefulness of NUDT15 genotyping as a pharmacogenomic test for thiopurine has been established. The first such test developed to date, NUDT15 genotyping was approved for reimbursement in Japan in February 2019 for all indicated patients. We retrospectively examined claims data in Japan and confirmed that the proportion of patients who undergo genotyping before initiating a new thiopurine regimen has increased; furthermore, genotyping has improved the rate of treatment continuation and reduced on-treatment hospitalization. However, the genotyping rate before thiopurine induction was >50% for patients with inflammatory bowel disease and <20% for those with other immune-related diseases, indicating significant variation by disease field. Additionally, over 10% of tests were found to have been performed inappropriately, such as multiple genotyping of the same patient or testing more than 2 weeks after starting treatment. Although NUDT15 genotyping for patients requiring thiopurine treatment has been shown to improve thiopurine treatment continuation rate, measures are required to address the systematic issues identified in our analysis.
NUDT15基因分型作为硫嘌呤类药物的药物基因组学检测方法的有效性已得到确立。NUDT15基因分型是迄今为止开发的首个此类检测方法，于2019年2月在日本获批用于所有适应症患者的报销。我们回顾性研究了日本的理赔数据，证实了在开始新的硫嘌呤类药物治疗方案之前接受基因分型的患者比例有所增加；此外，基因分型提高了治疗持续率并减少了治疗期间的住院率。然而，炎症性肠病患者在硫嘌呤类药物诱导前的基因分型率>50%，而其他免疫相关疾病患者的基因分型率<20%，这表明不同疾病领域存在显著差异。此外，发现超过10%的检测存在不当操作，例如对同一患者进行多次基因分型或在开始治疗后2周以上进行检测。尽管已证明对需要硫嘌呤类药物治疗的患者进行NUDT15基因分型可提高硫嘌呤类药物的治疗持续率，但仍需要采取措施解决我们分析中发现的系统性问题。
