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

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.

FIGURE 1.

Changes in biomarkers with vedolizumab therapy. In patients with baseline biomarkers before vedolizumab therapy, s-TNF concentrations (A) decreased at week 26. s-α4β7 and s-MAdCAM-1 significantly changed at every time point measured (B). s-AA concentrations (C) significantly decreased at week 14 and trended toward lower concentrations at week 26, with lower sample sizes than previous time points (Supplementary Table 1). s-VCAM-1 changed at weeks 6 and 14, but these changes did not persist later during maintenance at week 26 (D).

FIGURE 2.

Biomarker trends over time by clinical remission. Using a linear mixed effects model, each biomarker (s-TNF (A), s-α4β7 (B), s-MAdCAM-1 (C), CRP (D), s-AA (E), s-ICAM-1 (F), s-VCAM-1 (G)) and vedolizumab concentrations (H) were compared over time between patients who achieved clinical remission in maintenance and those who did not. A significant interaction between time and clinical remission was observed with s-α4β7 (P = 0.044), s-MAdCAM-1 (P = 0.006), and s-VCAM-1 (P = 0.001), with s-α4β7 increasing faster in those who achieved clinical remission and s-MAdCAM-1 and s-VCAM-1 decreasing faster in those who achieved clinical remission. This was not observed with s-TNF (P = 0.22), CRP (P = 0.44), S-AA (P = 0.07), s-ICAM-1 (P = 0.07), or vedolizumab concentrations (P = 0.49).

FIGURE 3.

Biomarker trends over time by endoscopic remission. Using a linear mixed effects model, each biomarker (s-TNF (A), s-α4β7 (B), s-MAdCAM-1 (C), CRP (D), S-AA (E), s-ICAM-1 (F), s-VCAM-1 (G)) and vedolizumab concentrations (H) were compared over time between patients who achieved endoscopic remission in maintenance and those who did not. A significant interaction between time and endoscopic remission with s-MAdCAM-1 (P = 0.005), s-ICAM-1 (P = 0.014), and s-VCAM-1 (P < 0.001) was found, with each decreasing faster in those who achieved endoscopic remission. A trend for this was found with s-TNF concentrations (P = 0.052) and s-α4β7 (P = 0.07), but not for CRP (P = 0.075), SSA (P = 0.14), or vedolizumab (P = 0.47) concentrations.