Abstract

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

Battat R1, Dulai PS1, Vande Casteele N1, Evans E1, Hester KD2, Webster E2, Jain A2, Proudfoot JA3, Mairalles A1, Neill J1, Singh S1, Chang JT1, Rivera-Nieves J1, Sandborn WJ1, Boland BS1. Inflamm Bowel Dis. 2018 Oct 5. doi: 10.1093/ibd/izy307. [Epub ahead of print]
 
     

Author information

1 Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Center, University of California, San Diego, La Jolla, California.

2 Prometheus Laboratories Inc., San Diego, California.

3 Clinical and Translational Research Institute, University of California, San Diego, La Jolla, California.

Abstract

BACKGROUND: Vedolizumab inhibits α4β7-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.

METHODS: Prospectively scored maintenance clinical (26.5 weeks; interquartile range [IQR], 16.3-37.0 weeks) and endoscopic (23.5 weeks; IQR, 16.8-35.6 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.

RESULTS: Thirty-two patients were included. Soluble (s)-tumor necrosis factor (TNF)-α, s-α4β7, 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-α4β7 (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-α4β7 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.

CONCLUSION: Serum biomarkers were associated with outcomes in vedolizumab-treated UC patients. s-α4β7 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-α4β7 concentrations were higher in remitters.

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