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 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.

Optimizing Therapies Using Therapeutic Drug Monitoring: Current Strategies and Future Perspectives

“…Furthermore, patients with biochemical response, as measured by FCal (P < .01), and endoscopic response (P ¼ .04) had higher tissue levels of VDZ than patients who did not respond. 98 In the latter study, VDZ tissue concentrations were lower in nonresponders than in responders (0.07 vs 0.11 mg/mg, P ¼ .04). In the subgroup of patients with adequate VDZ serum concentrations (>14.6 mg/mL), tissue levels were not significantly different between responders and nonresponders (0.15 vs 0.13 mg/mg; P ¼ 0.92).…”

“…47 In addition, two recent studies investigated mucosal drug levels of VDZ, examining a mixed population of patients with IBD sampled at different points in the treatment cycle as well as 1 study in patients with UC systematically sampled at week 14. 98,99 Serum and tissue drug concentrations were correlated in both studies (r 2 ¼ 0.83; P < .0001). In the former study, mucosal VDZ levels correlated with endoscopic response (P ¼ .06), unlike serum levels.…”

Modulation of Indoleamine 2,3-Dioxygenase 1 During Inflammatory Bowel Disease Activity in Humans and Mice

“…We prospectively included patients starting treatment with either the anti-α4β7 integrin antibody VDZ (inhibiting lymphocyte trafficking to the gut mucosa), or the anti-p40 antibody UST (blocking the IL12/IL23 signaling involved in IBD pathogenesis). 40 Overall, samples from 93 patients affected by IBD with a median disease duration of 14.3 years (IQR 7-18) at week 16 of the pharmacological treatment (namely, n = 37 treated with VDZ and n = 56 treated with UST) were analyzed ( Table 2 ). In total, 87/93 (94%) patients were previously exposed to ⩾1 anti-TNFα drugs before starting VDZ or UST, of whom 79/87 (91%) were anti-TNFα-refractory, defined as having primary non-response or secondary loss of response, and 8/87 (9%) stopped anti-TNFα because of adverse effects.…”

Therapeutic Drug Monitoring of Vedolizumab in Inflammatory Bowel Disease Patients during Maintenance Treatment—TUMMY Study

“…To understand this mechanism, in a small study with 37 patients, the correlation between tissue and serum VDZ concentration and their association with mucosal inflammation and response to VDZ were evaluated: patients with higher tissue exposure had better biochemical and endoscopic outcomes. Additionally, these tissue concentrations were higher than theoretically needed for receptor saturation [ 30 ].…”