英夫利昔单抗维持治疗期间炎症性肠病患者的年度治疗药物监测：平衡疗效与药代动力学失败风险

Annual Therapeutic Drug Monitoring in Patients with Inflammatory Bowel Disease During Infliximab Maintenance Therapy: Balancing Efficacy with Risk of Pharmacokinetic Failure.

作者信息

Lim Yujin, Park Boram, Jeon Kyeongman, Jeong Ok Soon, Kim Eun Ran, Kim Young-Ho, Chang Dong Kyung, Hong Sung Noh

机构信息

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea.

Biomedical Statistics Center, Samsung Medical Center, Research Institute for Future Medicine, Seoul, Korea.

出版信息

Dig Dis Sci. 2025 Apr 29. doi: 10.1007/s10620-025-09032-9.

DOI:10.1007/s10620-025-09032-9

PMID:40299290

Abstract

BACKGROUND AND AIMS

Recent studies indicate that proactive therapeutic drug monitoring (TDM) can improve clinical outcomes in patients with inflammatory bowel disease (IBD) treated with infliximab. Repetitive infliximab trough level (IFX TL) measurements for proactive TDM may increase patient inconvenience and medical costs. Therefore, we aimed to determine the optimal interval for TDM during infliximab maintenance therapy in patients with IBD.

METHODS

A prospective cohort study was performed on the patients with IBD who were in clinical remission on infliximab maintenance therapy and had IFX TL ≥ 3 μg/mL after one-time dose optimization. Infliximab TL were measured before each infliximab infusion to identify the pharmacokinetic (PK) relapse (two consecutive IFX TL < 3 μg/mL). Kaplan-Meier method was used to calculate the time to PK relapse.

RESULTS

A total of 103 patients were enrolled and followed for a median of 18.5 months. PK relapse occurred in 19 patients (18.5%), with a higher rate of PK relapse in patients with IFX TL 3-5 μg/mL (16/60, 26.7%) compared to those with IFX TL ≥ 5 μg/mL (3/43, 7.0%). Kaplan-Meier survival time to maintain 95%, 90%, 85%, 80%, and 75% therapeutic IFX TL persistence rate without PK relapse was 4.1, 10.3, 13.3, 14.3, and 19.8 months, respectively. Log-rank test showed that therapeutic IFX TL persistence rates were significantly lower in patients with IFX TL 3-5 μg/mL group compared to those with IFX TL ≥ 5 μg/mL group (p = 0.010). Kaplan-Meier retention time to maintain 85% therapeutic IFX TL persistence rate without PK relapse was 10.3 months in IFX TL 3-5 μg/mL group and 20.2 months in IFX TL ≥ 5 μg/mL group, respectively.

CONCLUSIONS

Proactive TDM measuring with IFX TL annually may be helpful in maintaining therapeutic IFX TL ≥ 3 μg/mL in 85% of patients with IBD and clinical remission on infliximab maintenance therapy.

摘要

背景与目的

近期研究表明，对于接受英夫利昔单抗治疗的炎症性肠病（IBD）患者，积极的治疗药物监测（TDM）可改善临床结局。为进行积极的TDM而重复测量英夫利昔单抗谷浓度（IFX TL）可能会增加患者的不便和医疗费用。因此，我们旨在确定IBD患者在英夫利昔单抗维持治疗期间TDM的最佳间隔时间。

方法

对接受英夫利昔单抗维持治疗且临床缓解、单次剂量优化后IFX TL≥3μg/mL的IBD患者进行一项前瞻性队列研究。在每次英夫利昔单抗输注前测量IFX TL，以确定药代动力学（PK）复发（连续两次IFX TL<3μg/mL）。采用Kaplan-Meier法计算至PK复发的时间。

结果

共纳入103例患者，中位随访时间为18.5个月。19例患者（18.5%）发生PK复发，IFX TL为3 - 5μg/mL的患者PK复发率（16/60，26.7%）高于IFX TL≥5μg/mL的患者（3/43，7.0%）。维持95%、90%、85%、80%和75%治疗性IFX TL持续率且无PK复发的Kaplan-Meier生存时间分别为4.1、10.3、13.3、14.3和19.8个月。对数秩检验显示，IFX TL为3 - 5μg/mL组的治疗性IFX TL持续率显著低于IFX TL≥5μg/mL组（p = 0.010）。IFX TL为3 - 5μg/mL组和IFX TL≥5μg/mL组维持85%治疗性IFX TL持续率且无PK复发的Kaplan-Meier保留时间分别为10.3个月和20.2个月。