Kim Eun Sil, Kwon Yiyoung, Choe Yon Ho, Kim Mi Jin
Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Therap Adv Gastroenterol. 2023 May 6;16:17562848231170948. doi: 10.1177/17562848231170948. eCollection 2023.
Immunogenicity to antitumor necrosis factor alpha agents, such as infliximab (IFX), may lead to therapeutic failure.
This study evaluated the relationship between free and total antibodies-to-infliximab (ATIs), trough levels (TLs) of IFX, and the response to dose intensification.
We performed a prospective, observational study including pediatric patients with Crohn's disease (CD) receiving IFX maintenance therapy without dose intensification.
We compared clinical and laboratory outcomes according to the presence of free and total ATIs. Factors associated with response to IFX dose intensification were investigated by analyzing IFX TLs and free and total ATIs.
Of the 98 patients, 9 patients had detectable free ATIs and 38 patients had total ATIs. Patients with free ATIs had significantly lower TLs (0.7 5.1 µg/mL, < 0.001) than patients without free ATIs. However, there was no difference in the IFX TLs according to the presence of total ATIs ( = 0.2523). Analysis of the 38 samples with total ATIs showed that response to dose intensification was significantly lower in patients with free ATIs than those without free ATIs (22.2% 65.5%, < 0.001). In addition, free ATIs were the only factor with poor response to dose intensification [odds ratio (OR): 14.15, 95% confidence interval (CI): 1.31-151.97, = 0.0140]. According to the receiver operating characteristic analysis, the optimal cutoff level indicating non-response to IFX dose intensification was 30.0 AU/mL for free ATIs concentration (area under curve, 0.792; 95% CI: 0.590-0.942; sensitivity, 60.0%; specificity, 96.7%; = 0.0241).
Free ATIs, but not total ATIs, have a negative impact on the course of CD. Free ATIs are potential reliable biomarker for predicting the effect of dose intensification in patients with loss of response to IFX. Future studies based on serial and proactive therapeutic drug monitoring are required in the future.
对抗肿瘤坏死因子α药物（如英夫利昔单抗（IFX））产生免疫原性可能导致治疗失败。
本研究评估游离和总英夫利昔单抗抗体（ATIs）、IFX谷浓度（TLs）与剂量强化反应之间的关系。
我们进行了一项前瞻性观察性研究，纳入接受IFX维持治疗且未进行剂量强化的克罗恩病（CD）儿科患者。
我们根据游离和总ATIs的存在情况比较临床和实验室结果。通过分析IFX TLs以及游离和总ATIs来研究与IFX剂量强化反应相关的因素。
98例患者中，9例可检测到游离ATIs，38例可检测到总ATIs。有游离ATIs的患者的TLs（0.7±5.1μg/mL，P<0.001）显著低于无游离ATIs的患者。然而，根据总ATIs的存在情况，IFX TLs并无差异（P=0.2523）。对38份有总ATIs的样本分析显示，有游离ATIs的患者对剂量强化的反应显著低于无游离ATIs的患者（22.2%对65.5%，P<0.001）。此外，游离ATIs是对剂量强化反应不佳的唯一因素[比值比（OR）：14.15，95%置信区间（CI）：1.31 - 151.97，P = 0.0140]。根据受试者工作特征分析，游离ATIs浓度表明对IFX剂量强化无反应的最佳截断水平为30.0 AU/mL（曲线下面积，0.792；95%CI：0.590 - 0.942；敏感性，60.0%；特异性，96.7%；P = 0.0241）。
游离ATIs而非总ATIs对CD病程有负面影响。游离ATIs是预测对IFX反应丧失患者剂量强化效果的潜在可靠生物标志物。未来需要基于连续和主动治疗药物监测的进一步研究。
