Long Cai-Yun, Huang Ying
Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Front Pharmacol. 2025 Mar 26;16:1558897. doi: 10.3389/fphar.2025.1558897. eCollection 2025.
Despite the emergence of numerous innovative targeted therapies for the management of pediatric inflammatory bowel disease (IBD), azathioprine continues to be a pivotal first-line therapeutic agent. Nonetheless, the considerable frequency of myelosuppression associated with its use warrants careful consideration and further investigation. This study aims to investigate the application of pharmacogenomics in Chinese pediatric IBD treated with azathioprine, and to elucidate its association with the occurrence of myelosuppression.
We conducted a retrospective analysis to determine the prevalence of pharmacogenetic abnormalities and thiopurine-induced myelosuppression in Chinese pediatric patients with IBD.
Among the 227 patients underwent pharmacogenetic testing, abnormal genetypes occurred in 66 patients, among which 7 patients exhibited aberrant and 59 had aberrant . Of the 58 patients who were treated with azathioprine, 23 cases experienced myelosuppression. All three children with heterozygous mutations in developed leukopenia following azathioprine treatment. Among patients with normal pharmacogenetic results, 20 cases (36.4%) developed myelosuppression, while 35 cases (63.6%) did not. The dose of azathioprine was below the recommended level in guidelines. The mean dose of azathioprine (mg/kg/day) in the myelosuppression group was 1.22 ± 0.32, compared to 1.42 ± 0.42 in the non-myelosuppression group, which represented a statistically significant difference (p < 0.05). Age, gender, and the use of concomitant biologics, mesalazine, or glucocorticoids did not show significant differences between the groups (p > 0.05).
C415T is prevalent in China and is associated with an increased risk of azathioprine-induced myelosuppression. A reduced dose of azathioprine should be considered for Chinese pediatric patients with IBD, even in those with normal pharmacogenetic profiles.
尽管出现了众多用于治疗儿童炎症性肠病（IBD）的创新靶向疗法，但硫唑嘌呤仍然是关键的一线治疗药物。然而，与其使用相关的骨髓抑制发生率较高，值得仔细考虑并进一步研究。本研究旨在探讨药物基因组学在中国接受硫唑嘌呤治疗的儿童IBD中的应用，并阐明其与骨髓抑制发生的关联。
我们进行了一项回顾性分析，以确定中国儿童IBD患者中药物遗传异常和硫嘌呤诱导的骨髓抑制的患病率。
在227例接受药物基因检测的患者中，66例出现异常基因型，其中7例表现为异常 ，59例表现为异常 。在58例接受硫唑嘌呤治疗的患者中，23例发生骨髓抑制。所有3例 杂合突变的儿童在接受硫唑嘌呤治疗后均出现白细胞减少。在药物基因检测结果正常的患者中，20例（36.4%）发生骨髓抑制，而35例（63.6%）未发生。硫唑嘌呤的剂量低于指南推荐水平。骨髓抑制组硫唑嘌呤的平均剂量（mg/kg/天）为1.22±0.32，非骨髓抑制组为1.42±0.42，差异有统计学意义（p<0.05）。年龄、性别以及同时使用生物制剂、美沙拉嗪或糖皮质激素在两组之间未显示出显著差异（p>0.05）。
C415T在中国很常见，并且与硫唑嘌呤诱导的骨髓抑制风险增加有关。对于中国儿童IBD患者，即使是药物基因检测结果正常的患者，也应考虑降低硫唑嘌呤的剂量。
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