背景:这项研究评估了NUDT15密码子139基因分型在优化日本炎症性肠病(IBD)的硫代嘌呤治疗中的有效性,使用真实世界的数据,并旨在建立基于基因型的治疗策略。
方法:对4628例接受NUDT15密码子139基因分型的IBD患者进行回顾性分析。这项研究评估了基因分型测试的目的以及获得的结果后的后续处方。结果在基因分型组(有基因分型试验的硫嘌呤)和非基因分型组(无基因分型试验的硫嘌呤)之间进行比较。通过基因型和先前的基因分型状态分析不良事件(AE)的危险因素。
结果:用于医学目的的基因分型试验显示,Arg/Arg和Arg/Cys基因型之间的硫嘌呤诱导率没有显着差异,但有9名Arg/Cys患者选择退出噻嘌呤治疗。在基因分型组中,Arg/Arg患者接受的初始剂量高于非基因分型组,而Arg/Cys患者接受的Arg/Cys较低(中位数25mg/天)。基因分型组中发生的AE较少,因为它们在Arg/Cys病例中的发生率较低。从<25mg/天的AZA开始减少Arg/Cys患者的AE,而Arg/Arg患者在维持≥75mgAZA时保留率更好。恶心和肝损伤与硫代嘌呤制剂相关,但与剂量无关。pH依赖性美沙拉嗪降低了美沙拉嗪使用者白细胞减少的风险。
结论:NUDT15密码子139基因分型可有效减少基于基因型的剂量调整后,IBD患者的噻嘌呤诱导的AE并改善治疗保留率。这项研究提供了基于基因型的数据驱动的治疗策略,并确定了特定AE的风险因素。有助于精制硫嘌呤治疗方法。
This
study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies.
A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This
study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status.
Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users.
NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This
study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.