Vedolizumab Tissue Concentration Correlates to Mucosal Inflammation and Objective Treatment Response in Inflammatory Bowel Disease

Abstract Background The association between vedolizumab (VDZ) exposure and treatment response is unclear and seems insufficiently explained by serum levels. The aim of this study was to assess the correlation between VDZ concentrations in serum and intestinal tissue and their association with mucosa...

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Published in:Inflammatory bowel diseases 2021-10, Vol.27 (11), p.1813-1820
Main Authors: Pauwels, Renske W M, Proietti, Elisa, van der Woude, Christien J, Oudijk, Lindsey, Crombag, Marie-Rose B S, Peppelenbosch, Maikel P, Grohmann, Ursula, Fuhler, Gwenny M, de Vries, Annemarie C
Format: Article
Language:English
Subjects:
Adult
Antibodies, Monoclonal, Humanized - therapeutic use
Basic Science Research
Gastrointestinal Agents - therapeutic use
Humans
Inflammation - drug therapy
Inflammatory Bowel Diseases - drug therapy
Intestinal Mucosa - pathology
Prospective Studies
Treatment Outcome
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Summary:Abstract Background The association between vedolizumab (VDZ) exposure and treatment response is unclear and seems insufficiently explained by serum levels. The aim of this study was to assess the correlation between VDZ concentrations in serum and intestinal tissue and their association with mucosal inflammation and response to VDZ. Methods This prospective study included 37 adult patients with inflammatory bowel disease with endoscopic inflammation at baseline who started VDZ. At week 16, serum and biopsies were collected for VDZ measurement by enzyme-linked immunosorbent assay. Nonlinear mixed-effects modeling was used to calculate serum trough concentrations and to assess intestinal tissue concentrations. Validated clinical and endoscopic scores were used to define clinical and endoscopic response and remission, and fecal calprotectin levels were used to assess biochemical response. Histologic remission was determined by the Nancy score. Results A positive correlation was observed between VDZ concentrations in serum and tissue (r2 = 0.83; P < 0.0001). High mucosal rather than serum VDZ levels correlated with a reduced endoscopic (P = 0.06) grade of mucosal inflammation. Furthermore, patients with a positive biochemical and endoscopic outcome had higher tissue levels of VDZ than patients without biochemical and endoscopic response (P < 0.01 and P = 0.04, respectively). Conclusions Tissue levels of VDZ may provide a better marker than serum levels for mucosal inflammation and objective treatment outcome at week 16. The potential of VDZ tissue levels for therapeutic drug monitoring in inflammatory bowel disease warrants further exploration.
ISSN:1078-0998
1536-4844
DOI:10.1093/ibd/izab053