Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, Amsterdam, the Netherlands.
Inflamm Bowel Dis. 2024 Oct 3;30(10):1678-1685. doi: 10.1093/ibd/izad307.
The use of concomitant azathioprine may improve efficacy and pharmacokinetic (PK) properties of infliximab (IFX) but is also associated with an increased risk of adverse events. Proactive therapeutic drug monitoring (pTDM) of IFX monotherapy is an alternative strategy to improve PK. The aim of this study was to evaluate whether IFX with an immunomodulator (combo) has PK benefits over IFX-pTDM (mono) in pediatric Crohn's disease (CD).
This PK analysis included pediatric CD patients who started either IFX combo (TISKids study) or IFX mono with pTDM (REFINE cohort). Combo and mono IFX trough levels (TLs) and antibodies-to-infliximab were assessed at infusion 3, 4, and 5. A population PK model was built to compare IFX PK outcomes (clearance [CL], TLs and cumulative exposure) between combo and mono groups at infusion 4 and 5. Clinical response and steroid-free clinical remission (SFCR) was assessed at infusion 4 and 5.
This study included 128 pediatric CD patients (66 mono and 62 combo). At infusion 5, there was no significant difference between mono and combo median TLs 4.1 µg/mL (2.1, 7.8) vs 5.9 µg/mL (3.2, 9.4; P = .14) or median CL 0.26 L/d (0.21, 0.32) vs 0.26 L/d (0.21, 0.33; P = .81). Mono patients had a lower SFCR rate at infusion 5 (53% [31 of 59] vs 80% [32 of 40]; P = .01). Clinical response rates were significantly higher among combo than mono patients at both infusion 4 and 5.
This study suggests that there are no PK differences (TLs and CL) between combo and mono therapy in pediatric CD patients who started IFX.
联合使用硫唑嘌呤可提高英夫利昔单抗（IFX）的疗效和药代动力学（PK）特性，但也会增加不良事件的风险。英夫利昔单抗单药治疗的主动治疗药物监测（pTDM）是改善 PK 的另一种策略。本研究旨在评估在儿童克罗恩病（CD）患者中，IFX 联合免疫调节剂（联合治疗）是否比 IFX-pTDM（单药治疗）具有更好的 PK 获益。
本 PK 分析纳入了开始接受 IFX 联合治疗（TISKids 研究）或 IFX-pTDM 单药治疗（REFINE 队列）的儿童 CD 患者。在第 3、4 和 5 次输注时评估联合治疗和单药治疗的 IFX 谷浓度（TLs）和抗英夫利昔单抗抗体。建立群体 PK 模型以比较联合和单药治疗组在第 4 和 5 次输注时 IFX 的 PK 结局（清除率 [CL]、TLs 和累积暴露）。在第 4 和第 5 次输注时评估临床应答和无激素临床缓解（SFCR）。
本研究纳入了 128 例儿童 CD 患者（单药治疗 66 例，联合治疗 62 例）。在第 5 次输注时，单药和联合治疗的中位数 TLs 分别为 4.1μg/mL（2.1，7.8）和 5.9μg/mL（3.2，9.4；P =.14），中位 CL 分别为 0.26 L/d（0.21，0.32）和 0.26 L/d（0.21，0.33；P =.81），差异均无统计学意义。单药治疗组在第 5 次输注时的 SFCR 率较低（53%[31/59] vs. 80%[32/40]；P =.01）。联合治疗组在第 4 和第 5 次输注时的临床应答率均显著高于单药治疗组。
本研究表明，在开始接受 IFX 治疗的儿童 CD 患者中，联合治疗与单药治疗在 TLs 和 CL 方面无差异。
