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Tissue Exposure does not Explain Non-Response in Ulcerative Colitis Patients with Adequate Serum Vedolizumab
Nathalie Van den Berghe1, Bram Verstockt2,3, Ann Gils1
1Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Background And Aims:
Some patients with ulcerative colitis [UC] do not respond to vedolizumab treatment despite adequate drug exposure in serum. This study aimed to investigate vedolizumab in tissue and questioned whether insufficient tissue exposure could explain non-response in UC patients with adequate serum vedolizumab concentrations.
Methods:
A paired serum sample and colonic mucosal biopsy was collected from 40 UC patients [20 endoscopic responders, 20 non-responders] at week 14 of vedolizumab treatment. Vedolizumab, soluble [s]-mucosal addressin cell adhesion molecule-1 [MAdCAM-1], s-vascular cell adhesion molecule-1 [VCAM-1] and s-intercellular adhesion molecule-1 [ICAM-1] were measured in serum and/or tissue. Endoscopic response was defined as Mayo endoscopic sub-score ≤1.
Results:
A significant positive correlation was observed between vedolizumab serum and colonic tissue concentrations [ρ = 0.84, p < 0.0001], regardless of the macroscopic inflammatory state of the tissue. Vedolizumab tissue concentrations were lower in non-responders than in responders [0.07 vs 0.11 µg/mg, p = 0.04]. In the subgroup of patients with adequate vedolizumab serum concentrations [>14.6 µg/mL], tissue vedolizumab was not significantly different between responders and non-responders [0.15 vs 0.13 µg/mg; p = 0.92]. Serum sMAdCAM-1 concentrations, but not serum sICAM-1 or sVCAM-1 concentrations, were significantly higher in responders than in non-responders with adequate vedolizumab serum concentrations [1.04 vs 0.83 ng/mL, p = 0.03].
Conclusions:
Vedolizumab concentrations in colonic mucosal tissue of UC patients reflect the concentration in serum regardless of the macroscopic inflammatory state of the tissue. Our data show that insufficient tissue exposure does not explain non-response in UC patients with adequate serum vedolizumab concentrations.
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