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

TitleBiomarkers Are Associated With Clinical and Endoscopic Outcomes With Vedolizumab Treatment in Ulcerative Colitis.
Publication TypeJournal Article
Year of Publication2019
AuthorsBattat R, Dulai PS, Casteele NVande, Evans E, Hester KD, Webster E, Jain A, Proudfoot JA, Mairalles A, Neill J, Singh S, Chang JT, Rivera-Nieves J, Sandborn WJ, Boland BS
JournalInflamm Bowel Dis
Date Published2019 01 10

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.

Alternate JournalInflamm. Bowel Dis.
PubMed ID30295781
PubMed Central IDPMC6327228
Grant ListKL2 TR001444 / TR / NCATS NIH HHS / United States
UL1 TR001442 / TR / NCATS NIH HHS / United States