期刊
INFLAMMATORY BOWEL DISEASES
卷 25, 期 2, 页码 410-420出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/ibd/izy307
关键词
vedolizumab; ulcerative colitis; biomarkers; personalized medicine
资金
- National Institutes of Health (NIH) [UL1TR001442]
- National Center for Advancing Translational Sciences (NCATS), a part of the National Institutes of Health (NIH)
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.
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