Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan.
Division for Evaluation and Analysis of Drug Information, Faculty of Pharmacy, Keio University, Shibakoen, Minato-ku, Tokyo, Japan.
PLoS One. 2018 Oct 4;13(10):e0204632. doi: 10.1371/journal.pone.0204632. eCollection 2018.
Since anti-tumor necrosis factor (TNF)-α agents (TNF-α inhibitors) induce both clinical response and remission in patients with moderate to severe inflammatory bowel disease (IBD), the use of anti-TNF therapies has fundamentally changed the approach to treatment for patients with IBD. Infliximab (IFX) is a TNF-α inhibitor approved for the induction and remission of Crohn's disease (CD). However, even among patients who initially demonstrate a clinical response to IFX therapy, secondary loss of response occurs, although the reason remains unknown. We therefore investigated predictive factors associated with the response to IFX in long-term maintenance treatment in Japanese CD patients. Eight types of single-nucleotide polymorphisms (SNPs) were investigated using the real-time PCR method, and patient characteristics were collected from the electronic medical records. The Crohn's Disease Activity Index criteria were used as the response to IFX therapy. The observation period was 1 year after IFX had been administered for more than 1 year. Associations between the IFX response and patient characteristics were evaluated using the multivariate logistic regression model. We studied 121 unrelated adult Japanese with CD treated for more than 1 year with IFX as outpatients at Keio University Hospital from November 1, 2014 to November 30, 2015. Among them, 71 were classified as in remisson. In multivariate analysis, patients with the TNF-α 857C>T C/C genotype, shorter disease duration, without double dosing, and combination treatment with an immunomodulator had higher remisson rates than those with the C/T or T/T genotype, longer disease duration, with double dosing, and no combination treatment with an immunomodulator. The response to IFX in Japanese CD patients may therefore be predicted by these 4 characteristics in actual clinical practice.
由于抗肿瘤坏死因子 (TNF)-α 制剂(TNF-α 抑制剂)可诱导中重度炎症性肠病(IBD)患者的临床缓解和缓解,因此抗 TNF 治疗已从根本上改变了 IBD 患者的治疗方法。英夫利昔单抗(IFX)是一种批准用于诱导和缓解克罗恩病(CD)的 TNF-α 抑制剂。然而,即使在最初对 IFX 治疗有临床反应的患者中,也会发生继发性无反应,尽管原因尚不清楚。因此,我们研究了日本 CD 患者长期维持治疗中与 IFX 反应相关的预测因素。使用实时 PCR 法研究了 8 种单核苷酸多态性(SNP),并从电子病历中收集了患者特征。使用克罗恩病活动指数标准作为 IFX 治疗的反应。观察期为 IFX 治疗 1 年以上后的 1 年。使用多变量逻辑回归模型评估 IFX 反应与患者特征之间的关联。我们研究了 2014 年 11 月 1 日至 2015 年 11 月 30 日期间在庆应义塾大学医院接受 IFX 治疗超过 1 年的 121 例无关成年日本 CD 患者。其中 71 例缓解。多变量分析显示,TNF-α857C>T C/C 基因型、较短的疾病病程、不加倍剂量和联合免疫调节剂治疗的患者缓解率高于 C/T 或 T/T 基因型、较长的疾病病程、加倍剂量和不联合免疫调节剂治疗的患者。因此,在实际临床实践中,这些 4 个特征可能可以预测日本 CD 患者对 IFX 的反应。