Biomarkers Are Associated With Clinical and Endoscopic Outcomes With Vedolizumab Treatment in Ulcerative Colitis

被引:29
作者
Battat, Robert [1 ]
Dulai, Parambir S. [1 ]
Vande Casteele, Niels [1 ]
Evans, Elisabeth [1 ]
Hester, Kelly D. [2 ]
Webster, Edvelyn [2 ]
Jain, Anjali [2 ]
Proudfoot, James A. [3 ]
Mairalles, Ara [1 ]
Neill, Jennifer [1 ]
Singh, Siddharth [1 ]
Chang, John T. [1 ]
Rivera-Nieves, Jesus [1 ]
Sandborn, William J. [1 ]
Boland, Brigid S. [1 ]
机构
[1] Univ Calif San Diego, Dept Med, Div Gastroenterol, Ctr Inflammatory Bowel Dis, La Jolla, CA 92093 USA
[2] Prometheus Labs Inc, San Diego, CA USA
[3] Univ Calif San Diego, Clin & Translat Res Inst, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
vedolizumab; ulcerative colitis; biomarkers; personalized medicine; INFLAMMATORY-BOWEL-DISEASE; ADHESION MOLECULES; CROHNS-DISEASE; MAINTENANCE THERAPY; INDUCTION THERAPY; ENDOTHELIAL RECEPTOR; TROUGH LEVELS; MUCOSAL; ANTIBODY; INTEGRIN;
D O I
10.1093/ibd/izy307
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Vedolizumab inhibits 47-mediated lymphocyte trafficking and is effective in ulcerative colitis (UC). This study evaluated drug and biomarker concentrations and patient outcomes during vedolizumab treatment in UC. Prospectively scored maintenance clinical (26.5 weeks; interquartile range [IQR], 16.337.0 weeks) and endoscopic (23.5 weeks; IQR, 16.835.6 weeks) outcomes were compared with serum vedolizumab concentrations, antivedolizumab antibodies, and serum biomarkers at baseline and weeks 2, 6, 14, and 26. A linear mixed-effects model compared biomarker trajectories over time between clinical and endoscopic remitters and nonremitters. Thirty-two patients were included. Soluble (s)tumor necrosis factor (TNF), s-47, s-mucosal addressin cell adhesion molecule (s-MAdCAM-1), and s-amyloid A (s-AA) significantly changed with treatment. A linear mixed-effects model demonstrated that s-47 (P = 0.044) increased and s-MAdCAM-1 (P = 0.006) and s-vascular cell adhesion molecule-1 (s-VCAM-1, P = 0.001) decreased more rapidly in patients achieving clinical remission in maintenance. S-MAdCAM-1 (P = 0.005), s-intracellular adhesion molecule-1 (ICAM-1; P = 0.014), s-VCAM-1 (P < 0.001), and s-TNF (P = 0.052) decreased more rapidly in endoscopic remitters. In clinical remitters, higher week 14 (20.3 ng/mL vs 6.0 ng/mL; P = 0.013) and week 26 (14.1 ng/mL vs 8.6 ng/mL; P = 0.05) s-47 were observed. In endoscopic remitters, week 2 (6.7 pg/mL vs 17.8 pg/mL; P = 0.038) and week 6 (3.9 pg/mL vs 15.6 pg/mL; P = 0.005) s-TNF and week 14 s-VCAM (589.1 ng/mL vs 746.0 ng/mL; P = 0.05) were lower. Serum biomarkers were associated with outcomes in vedolizumab-treated UC patients. s-47 increased, whereas s-MAdCAM-1, s-VCAM-1, s-ICAM-1, and s-TNF decreased more rapidly in remitters. At individual time points, induction s-TNF and maintenance s-VCAM-1 concentrations were lower, whereas maintenance s-47 concentrations were higher in remitters.
引用
收藏
页码:410 / 420
页数:11
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