Inflamm Bowel Dis. 2021 Mar 11;izab053. doi: 10.1093/ibd/izab053. Online ahead of print.

Renske W M Pauwels ¹, Elisa Proietti ^1 2, Christien J van der Woude ¹, Lindsey Oudijk ³, Marie-Rose B S Crombag ⁴, Maikel P Peppelenbosch ¹, Ursula Grohmann ², Gwenny M Fuhler ¹, Annemarie C de Vries ¹

Author information

• ¹Erasmus MC, Department of Gastroenterology and Hepatology, Rotterdam, the Netherlands.
• ²University of Perugia, Department of Experimental Medicine, Perugia, Italy.
• ³Erasmus MC, Department of Pathology, Rotterdam, the Netherlands.
• ⁴Erasmus MC, Department of Hospital Pharmacy, Rotterdam, the Netherlands.

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.