Theory-based analysis of anti-inflammatory effect of infliximab on Crohn's disease and rheumatoid arthritis
Theory-based analysis of anti-inflammatory effect of infliximab on Crohn's disease and rheumatoid arthritis
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DOI：
10.1007/s00296-010-1553-8
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发表时间：
2012-01-01
影响因子：
4
通讯作者：
Yamada, Yasuhiko
中科院分区：
文献类型：
--
作者：
Kimura, Koji;Takayanagi, Risa;Yamada, Yasuhiko
在日本，英夫利西单抗（IFX）治疗类风湿性关节炎（RA）和克罗恩病（CD）的推荐剂量方案不同。然而，这些差异并没有从理论上进行分析。在先前的研究中，我们构建了一个药代动力学-药效学模型来研究IFX对CD的作用，并发现它有助于为CD患者个体建立合理的IFX剂量方案。在本研究中，我们研究了基于理论的模型是否可以用于类风湿关节炎的情况下，也用它来评估剂量方案的有效性。我们的模型得到的结果与观察到的投标关节计数（TJC）的比率数据，这被认为是显示我们的分析的有效性，在很好的协议。因此，我们得出结论，该模型可用于RA患者。此外，在第一次输注后2周给予IFX的第二次给药对于在RA的早期阶段实现缓解是重要的。我们还比较了估计的RA与CD的药效学参数。RA的炎症消除速率常数大于CD，提示RA的炎症恢复快于CD，这可能是RA与CD剂量差异的原因之一。总之，根据肿瘤坏死因子（TNF）-α的个体定量因子使用我们的模型可以为个体患者建立IFX剂量方案。
In Japan, the recommended dosage regimens of infliximab (IFX) for treatment of rheumatoid arthritis (RA) and Crohn's disease (CD) are different. However, the differences have not been analyzed theoretically. In a previous study, we constructed a pharmacokinetic-pharmacodynamic model to investigate the effects of IFX for CD and found it useful to establish a rational dosage regimen of IFX for individual patients with CD. In the present study, we investigated whether the theory-based model could be used for cases of RA and also used it to evaluate the validity of the dosage regimen. The results obtained with our model were in good agreement with observed tender joint count (TJC) ratio data, which was considered to show the validity of our analysis. Thus, we concluded that the model could be used for patients with RA. Furthermore, a second administration of IFX given 2 weeks after the first infusion was important to achieve remission in the early stage of RA. We also compared the estimated pharmacodynamic parameters of RA with those of CD. The elimination rate constant of inflammation in RA was greater than that in CD, suggesting that the recovery from inflammation in RA is faster than that in CD, and indicating a reason for the difference in dosage between RA and CD. In conclusion, use of our model in light of the individual quantitative factor of tumor necrosis factor (TNF)-alpha allows establishment of IFX dosage regimens for individual patients.