Biomarkers are associated with clinical and endoscopic outcomes with vedolizumab treatment in Crohn's disease.
Biomarkers are associated with clinical and endoscopic outcomes with vedolizumab treatment in Crohn's disease.
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DOI：
10.1177/1756284820971214
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发表时间：
2020
影响因子：
4.2
通讯作者：
Boland BS
中科院分区：
文献类型：
--
作者：
Holmer AK;Battat R;Dulai PS;Vande Casteele N;Nguyen N;Jain A;Miralles A;Neill J;Le H;Singh S;Rivera-Nieves J;Sandborn WJ;Boland BS
Vedolizumab是一种α4β7整合素拮抗剂，是治疗克罗恩病(CD)的有效药物。需要生物标记物来指导治疗和预测结果。这项研究评估了接受vedolizumab治疗的CD患者的生物标记物浓度和结果。第0、2、6、14周和⩾26周的血清收集自接受维多利单抗治疗的难治性CD患者。观察血清中可溶性(S)-血管细胞黏附分子-1、S-细胞间黏附分子-1、S-粘膜地址素细胞黏附分子-1和S-α4-β-7整合素水平与内窥镜缓解的关系。共纳入22例CD患者。与治疗前比较，所有患者的S-α-1显著降低，S-MADCA4-β-7显著升高。缓解期患者S-血管细胞黏附分子-1和S-细胞间黏附分子-1的变化不同。在6周时，胃镜下获得缓解的患者的S-血管细胞间黏附分子-1(859.6 ng/ml对460.3 ng/ml，p = 0.03)和S-ICAM-1(545.7 ng/ml对286.2 ng/ml，p = 0.03)浓度的中位数高于未缓解的患者，而S-ICAM-1的浓度在临床缓解的患者中与未缓解的患者(669.1 ng/ml对291.0 ng/ml)有相似的差异。P = 0.04)。14周S-α-4、β-7在胃镜下获得缓解的患者浓度低于未缓解的患者(7.5 ng/ml对17.6 ng/ml，p = 0.020)。维多利单抗治疗后CD患者S-α-1显著降低，S-MADCAM-4、β-7显著升高。6周时S-细胞间黏附分子-1和S-血管细胞黏附分子-1浓度较高，14周时S-α4和β-7浓度较低，差异有统计学意义。这些发现可能有助于确定CD患者对vedolizumab治疗反应的早期预测因素。需要对不易治愈的CD患者进行进一步的验证。
Vedolizumab, an α4β7 integrin antagonist, is an effective therapy for Crohn’s disease (CD). Biomarkers are needed to guide therapy and predict outcomes. This study evaluated biomarker concentrations and outcomes in patients with CD undergoing vedolizumab treatment. Sera at weeks 0, 2, 6, 14, and ⩾26 were collected from vedolizumab-treated, refractory CD patients. Concentrations of soluble (s)-Vascular Cell Adhesion Molecule (VCAM)-1, s-Intercellular Cell Adhesion Molecule (ICAM)-1, s-Mucosal Addressin Cell Adhesion Molecule (MAdCAM)-1, and s-α4β7 integrin were evaluated for associations with achieving endoscopic remission. A total of 22 patients with CD were included. In all patients, s-MAdCAM-1 decreased significantly and s-α4β7 increased compared with baseline. s-VCAM-1 and s-ICAM-1 changed differentially in patients who achieved remission. At week 6, median s-VCAM-1 (859.6 ng/ml versus 460.3 ng/ml, p = 0.03) and s-ICAM-1 (545.7 ng/ml versus 286.2 ng/ml, p = 0.03) concentrations were higher in patients who achieved endoscopic remission compared with those who did not, and similar differences were observed for s-ICAM-1 concentrations in patients who achieved clinical remission, compared with those who did not (669.1 ng/ml versus 291.0 ng/ml, p = 0.04). Week 14 s-α4β7 concentrations were lower in patients who achieved endoscopic remission, compared with those who did not (7.5 ng/ml versus 17.6 ng/ml, p = 0.020). In all vedolizumab-treated CD patients, s-MAdCAM-1 decreased significantly and s-α4β7 increased. However, higher concentrations of s-ICAM-1 and s-VCAM-1 at week 6 and lower concentrations of s-α4β7 at week 14 differentiated patients who achieved endoscopic remission. These findings may help identify early predictors of response to vedolizumab treatment in patients with CD. Further validation in less refractory CD patients is needed.
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影响因子：
6.3
作者：
Goke, M;Hoffmann, JC;Manns, MP
通讯作者：
Manns, MP
DOI：
10.1124/jpet.109.153973
发表时间：
2009-09-01
影响因子：
3.5
作者：
Soler, Dulce;Chapman, Tobias;Fedyk, Eric R.
通讯作者：
Fedyk, Eric R.
影响因子：
7.3
作者：
Fuchs, Friederike;Schillinger, Daniela;Zundler, Sebastian
通讯作者：
Zundler, Sebastian
影响因子：
12.6
作者：
Ungar, Bella;Kopylov, Uri;Ben-Horin, Shomron
通讯作者：
Ben-Horin, Shomron
影响因子：
3.2
作者：
Rosario, Maria;Wyant, Timothy;Feagan, Brian G.
通讯作者：
Feagan, Brian G.