Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
Br J Clin Pharmacol. 2021 Oct;87(10):3776-3789. doi: 10.1111/bcp.14785. Epub 2021 Mar 27.
Controversies regarding infliximab treatment in elderly patients with inflammatory bowel diseases remain. We evaluated the effect of patient's age on infliximab exposure, efficacy and safety.
Retrospective case-control data of patients receiving infliximab induction treatment were analysed. A population pharmacokinetic model was developed to estimate individual pharmacokinetic parameters. A logistic regression model was used to investigate the effect of exposure on endoscopic remission. Repeated time-to-event models were developed to describe the hazard of safety events over time.
A total of 104 patients (46 elderly, ≥65 years) were included. A two-compartment population pharmacokinetic model with linear elimination adequately described the data. Infliximab clearance decreased with older age, higher serum albumin, lower fat-free mass, lower C-reactive protein and absence of immunogenicity. Yet, infliximab exposure was not significantly different between elderly and nonelderly. Regardless of age, an infliximab trough concentration at week (w)14 of 15.6 mg/L was associated with a 50% probability of attaining endoscopic remission between w6 and w22. Infliximab exposure during induction treatment was not a risk factor of (severe) adverse events. The hazard of severe adverse events and malignancy increased by 2% and 7%, respectively, with increasing year of age. Concomitant immunomodulator use increased the hazard of infection by 958%, regardless of age.
Elderly patients attained infliximab exposure and endoscopic remission similarly to nonelderly patients. Therefore, the same infliximab trough concentration target can be used in therapeutic drug monitoring. The hazards of severe adverse events and malignancy increased with age, but not with infliximab exposure.
关于老年炎症性肠病患者使用英夫利昔单抗治疗仍存在争议。我们评估了患者年龄对英夫利昔单抗暴露、疗效和安全性的影响。
分析了接受英夫利昔单抗诱导治疗的患者的回顾性病例对照数据。建立了群体药代动力学模型来估计个体药代动力学参数。使用逻辑回归模型研究了暴露对内镜缓解的影响。开发了重复时间事件模型来描述随时间安全事件的发生风险。
共纳入 104 例患者（46 例老年患者，≥65 岁）。具有线性消除的两室群体药代动力学模型可充分描述数据。英夫利昔单抗清除率随年龄增大、血清白蛋白升高、去脂体重降低、C 反应蛋白降低和无免疫原性而降低。然而，老年患者和非老年患者之间的英夫利昔单抗暴露并无显著差异。无论年龄大小，在第 14 周时英夫利昔单抗谷浓度为 15.6mg/L 时，在第 6 周到第 22 周之间有 50%的可能性达到内镜缓解。诱导治疗期间的英夫利昔单抗暴露不是（严重）不良事件的危险因素。严重不良事件和恶性肿瘤的发生风险分别增加 2%和 7%，与年龄增加相关。免疫调节剂的联合使用会使感染的发生风险增加 958%，无论年龄大小。
老年患者与非老年患者获得的英夫利昔单抗暴露和内镜缓解相似。因此，在治疗药物监测中可以使用相同的英夫利昔单抗谷浓度目标。严重不良事件和恶性肿瘤的发生风险随年龄增加而增加，但与英夫利昔单抗暴露无关。
