Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.
Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Gut. 2018 Jan;67(1):43-52. doi: 10.1136/gutjnl-2016-312293. Epub 2016 Oct 7.
Lymphocyte recruitment to the inflamed gut is increased in UC. Inhibition of this cell trafficking by vedolizumab (VDZ) was successful in inducing and maintaining remission and in induction of endoscopic mucosal healing. There are no data on histological healing with VDZ. We studied histological changes following VDZ therapy and compared gene expression in patients with UC before and after therapy.
Forty-one patients with UC from GEMINI I and LTS were studied before and at three time points (weeks 6/12/52) following VDZ therapy. Colonic biopsies were scored using the Geboes index and correlated with Mayo endoscopic subscore. Gene expression was analysed using Affymetrix gene arrays.
Fifty-five per cent of patients achieving endoscopic healing (= Mayo endoscopic subscore 0-1) with VDZ at the studied time points also had histological healing (= Geboes grade 0-1). In most healers, some residual histological changes (eg, disturbed architecture and increased mononuclear cell infiltrate) were still observed, although this was less at week 52. VDZ restored expression of many inflammatory genes in patients with endoscopic healing only at week 52 and not before. In VDZ healers, the expression of many genes remained dysregulated at weeks 6/12/52 compared with controls.
VDZ induces histological healing in >50% of patients with endoscopic healing, with maximal effect at week 52. VDZ also restored, although incompletely, the colonic expression of many immune-related genes in patients with UC achieving endoscopic healing at week 52. However, persistent histological and gene dysregulations did remain even in healers, suggesting that maintenance therapy will be necessary to control the intestinal inflammation.
NCT00783718 and NCT00790933; post-results.
溃疡性结肠炎（UC）患者的肠道炎症部位淋巴细胞募集增加。维得利珠单抗（VDZ）可抑制这种细胞迁移，从而成功诱导和维持缓解，并诱导内镜下黏膜愈合。但目前尚无 VDZ 治疗后组织学愈合的数据。我们研究了 VDZ 治疗后的组织学变化，并比较了 UC 患者治疗前后的基因表达。
本研究纳入 GEMINI I 和 LTS 研究中的 41 例 UC 患者，在 VDZ 治疗前及治疗后 6 周、12 周和 52 周时进行研究。采用 Geboes 指数对结肠活检进行评分，并与 Mayo 内镜评分进行相关性分析。采用 Affymetrix 基因芯片分析基因表达。
在研究的时间点，55%达到内镜缓解（= Mayo 内镜评分 0-1）的 VDZ 治疗患者也存在组织学缓解（= Geboes 分级 0-1）。在大多数缓解者中，尽管在第 52 周时程度较轻，但仍观察到一些残留的组织学改变（如，结构紊乱和单核细胞浸润增加）。仅在第 52 周时，VDZ 才恢复了内镜缓解患者的许多炎症基因表达，而在治疗前和治疗后 6 周和 12 周时则不能。在 VDZ 缓解者中，与对照组相比，许多基因的表达在治疗后 6 周、12 周和 52 周时仍存在失调。
VDZ 可诱导>50%的内镜缓解患者发生组织学缓解，在第 52 周时效果最大。在第 52 周时达到内镜缓解的 UC 患者中，VDZ 也恢复了许多免疫相关基因的结肠表达，尽管不完全。然而，即使在缓解者中，仍存在持续的组织学和基因失调，这表明为了控制肠道炎症，需要维持治疗。
NCT00783718 和 NCT00790933；post-results。
