P464 Vedolizumab concentrations in colonic mucosal tissue of ulcerative colitis patients inversely correlate with the severity of inflammation. (15th January 2020)

• Record Type: Journal Article
• Authors: Van den Berghe, N; Verstockt, B; Gils, A; Ferrante, M; Vermeire, S; Thomas, D
• Is Part Of: Journal of Crohn's and colitis. Volume 14(2020)Supplement 1
• Page Start: S411
• Page End: S412
• Publication Date: 2020-01-15
• Subjects: Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjz203.593
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background: Multiple studies have reported the association between vedolizumab serum concentrations and endoscopic outcomes in patients with ulcerative colitis (UC). However, little is known about drug consumption in tissue and the relationship with mucosal inflammation. This study aimed to investigate vedolizumab concentrations in the tissue of UC patients and the correlation with their inflammatory state and serum levels. Methods: A paired serum sample and colonic mucosal biopsy were collected in 36 UC patients at week 14 of vedolizumab treatment. In non-responders, defined as a Mayo endoscopic subscore of ≥2, inflamed colonic biopsies were taken in the sigmoid around 20–30 cm from the anal verge. In responders, defined as a Mayo endoscopic subscore ≤ 1, a biopsy was taken in a macroscopically uninflamed area at the same location. Biopsies were lysed by the addition of 10 μl lysis buffer (50 mM Tris, 0.1% Triton X-100 and 100 mM NaCl) per mg tissue and vortexed every 5 min during 1 h. Total protein content was measured and normalised to 3 mg/ml before analysis of the vedolizumab concentration using an in-house developed ELISA. Results are expressed as µg vedolizumab/mg total protein content. Results: A positive correlation was observed between vedolizumab concentrations in tissue and serum (Spearman r = 0.8447, p < 0.0001), both in inflamed ( r = 0.8609, p <0.0001, n = 16) and uninflamed tissue ( r = 0.7925, p <0.0001, n = 20). The median tissue vedolizumab concentration in patients with Mayo endoscopic subscore 0, 1, 2 and 3 were 0.120, 0.074, 0.062 and 0.064 μg/mg, respectively ( p < 0.01, see figure), indicating that tissue drug levels inversely correlate with the severity of inflammation. Vedolizumab tissue concentrations were significantly lower in non-responders compared with responders (0.064 vs. 0.112 μg/mg, p <0.05). Moreover, patients achieving Mayo endoscopic subscore 0 had significantly higher vedolizumab levels in colonic tissue compared with patients not achieving this outcome (0.120 vs. 0.065 μg/mg, p <0.02). Interestingly, a trend was observed towards higher serum-to-tissue ratios of vedolizumab in non-responders compared with responders ( p = 0.0523). This finding suggests that if two patients have the same serum vedolizumab concentration, the patient with mucosal inflammation is more likely to have lower tissue levels than the patient with no or limited inflammation. Conclusion: Vedolizumab concentrations in colonic mucosal tissue of UC patients inversely correlate with the severity of inflammation. As the serum-to-tissue ratio of vedolizumab is numerically higher in non-responders compared with responders, the relative distribution of vedolizumab in serum and tissue might be more important than the drug concentration alone.