Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Center for Gastroenterology and Inflammatory Bowel Disease, Ofuna Chuo Hospital, 6-2-24 Ofuna, Kamakura, Kanagawa 247-0056, Japan.
Eur J Pharm Sci. 2020 Jul 1;150:105317. doi: 10.1016/j.ejps.2020.105317. Epub 2020 Mar 20.
In infliximab (IFX) treatment for Crohn's disease (CD) and ulcerative colitis (UC), it is difficult to predict treatment failure during the induction phase. In the present study for optimal IFX treatment, we attempted to estimate serum IFX concentration and clinical response in individual patients during the induction phase to predict the indication of therapeutic effect and the possibility of treatment failure in the maintenance phase.
We estimated pharmacokinetic and pharmacodynamic (PK/PD) parameters and predicted the serum IFX concentration and clinical response using a PK/PD model and Markov chain Monte Carlo Bayesian analysis method during the induction phase. Then, we determined whether the indication of therapeutic effect between predicted and observed clinical response were matched during the maintenance phase.
Data obtained from 15 patients were analyzed. The correlation between predicted and observed values of serum IFX concentration (Pearson product-moment correlation coefficient, 0.700; P < 0.0001, n = 68) and clinical response of CD patients (0.790; P < 0.0001, n = 25) and UC patients (0.702; P = 0.0004, n = 21) were significantly high. The indication of therapeutic effect at the final time point of each patient (from day 115 to day 203) were successfully predicted in 14 of 15 patients (93.3%).
This study presents prediction of serum IFX concentration and clinical response in individual patients during induction therapy, with presumption of the indication of therapeutic effect and the treatment failure in the maintenance phase. Our results show the possibility of optimizing IFX therapy during the induction phase.
在英夫利昔单抗（IFX）治疗克罗恩病（CD）和溃疡性结肠炎（UC）时，在诱导期很难预测治疗失败。在本研究中，为了优化 IFX 治疗，我们试图在诱导期内估计个体患者的血清 IFX 浓度和临床反应，以预测治疗效果的指征和维持期治疗失败的可能性。
我们在诱导期内使用 PK/PD 模型和 Markov 链蒙特卡罗贝叶斯分析方法估计药代动力学和药效学（PK/PD）参数，并预测血清 IFX 浓度和临床反应。然后，我们确定在维持期内预测的临床反应和观察到的临床反应的治疗效果指征是否匹配。
对 15 例患者的数据进行了分析。血清 IFX 浓度的预测值与观察值之间的相关性（皮尔逊积矩相关系数，0.700；P<0.0001，n=68）和 CD 患者（0.790；P<0.0001，n=25）和 UC 患者（0.702；P=0.0004，n=21）的临床反应均显著高。在 15 例患者中的 14 例（93.3%）中，成功预测了每个患者的最终时间点（第 115 天至第 203 天）的治疗效果指征。
本研究在诱导治疗期间对个体患者的血清 IFX 浓度和临床反应进行了预测，推测了维持期的治疗效果指征和治疗失败的可能性。我们的结果表明，在诱导期优化 IFX 治疗的可能性。
