INSERM U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France.
Imelda GI Clinical Research Centre, Imeldaziekenhuis Bonheiden, Bonheiden, Belgium.
J Crohns Colitis. 2019 Aug 14;13(8):970-975. doi: 10.1093/ecco-jcc/jjz029.
Histological healing may be the ultimate therapeutic goal in ulcerative colitis [UC]. We investigated, for the first time, the association between vedolizumab trough levels and histological healing in UC.
This is a single-centre retrospective cohort study including all consecutive UC patients on vedolizumab maintenance therapy who had a histological evaluation blindly to clinical data and underwent therapeutic drug monitoring, between June 2014 and March 2018. Per-event analysis was performed. Histological healing was defined as a Nancy histological index ≤1.
Thirty-five histological samples were analysed. Median [interquartile range] vedolizumab trough levels were higher in the group with histological healing (31.5 [25-49.1] μg/mL) compared with the group without histological healing (15 [9-26.6] μg/mL, p = 0.02). The higher vedolizumab trough level quartiles tended to be associated with greater rates of histological healing [p = 0.10]. A cut-off vedolizumab trough level of 25 μg/mL predicted histological healing with an accuracy of 74% and an area under the receiver operating curve of 0.62 [95% confidence interval 0.58-0.92, p = 0.004]. Bivariate analysis identified a vedolizumab trough level ≥25 µg/mL [p = 0.006], a partial Mayo score ≤1 [p = 0.008], C-reactive protein level <5 mg/L [p = 0.005] and a Mayo endoscopic subscore ≤1 [p = 0.0004] as factors associated with histological healing.
Histological healing was associated with higher vedolizumab trough levels during maintenance therapy in UC. A vedolizumab trough level threshold of 25 μg/mL proved most optimal to predict histological healing according to the Nancy histological index. Confirmation of these data in larger, independent cohorts is needed.
组织学愈合可能是溃疡性结肠炎[UC]的最终治疗目标。我们首次研究了维得利珠单抗谷浓度与 UC 组织学愈合之间的关系。
这是一项单中心回顾性队列研究，纳入了 2014 年 6 月至 2018 年 3 月期间所有接受维得利珠单抗维持治疗且接受治疗药物监测的连续 UC 患者，这些患者的组织学评估对临床数据是盲法的。进行了按事件分析。组织学愈合定义为 Nancy 组织学指数≤1。
分析了 35 个组织学样本。与无组织学愈合组（15[9-26.6]μg/mL，p=0.02）相比，组织学愈合组的维得利珠单抗谷浓度中位数[四分位间距]更高（31.5[25-49.1]μg/mL）。较高的维得利珠单抗谷浓度四分位数似乎与更高的组织学愈合率相关[p=0.10]。维得利珠单抗谷浓度的截断值为 25μg/mL 预测组织学愈合的准确率为 74%，受试者工作特征曲线下面积为 0.62[95%置信区间 0.58-0.92，p=0.004]。二元分析确定了维得利珠单抗谷浓度≥25μg/mL[p=0.006]、部分 Mayo 评分≤1[p=0.008]、C 反应蛋白水平<5mg/L[p=0.005]和 Mayo 内镜亚评分≤1[p=0.0004]是与组织学愈合相关的因素。
在 UC 的维持治疗中，组织学愈合与较高的维得利珠单抗谷浓度相关。根据 Nancy 组织学指数，维得利珠单抗谷浓度阈值为 25μg/mL 时最能预测组织学愈合。需要在更大的独立队列中确认这些数据。
