Fecal loss of vedolizumab is associated with ulcerative colitis severity, lower serum vedolizumab levels, and rates of clinical response: Results from the FAVOUR study

Abstract

Background and Aims We conducted a prospective study (FAVOUR) of patients with ulcerative colitis (UC) commencing vedolizumab to investigate fecal vedolizumab loss and its impact on serum levels and treatment outcomes. Methods FAVOUR recruited patients with moderate-to-severe UC commencing vedolizumab. Fecal vedolizumab levels (FVL) were measured at days 1, 4, and 7 and at weeks 2, 6, and 14. Trough serum vedolizumab levels (SVL) were measured at weeks 2, 6, and 14. Results In total, 36 patients were recruited, of whom 33 completed induction therapy. Fecal vedolizumab was detectable in 80/203 (39%) samples. Statistically significant, positive correlations were observed between FVL and clinical, biochemical, baseline endoscopic, and histologic disease activity at day 1, 4, and 7 as well as weeks 2 and 6. Week 14 clinical non-responders had higher FVL than responders at that timepoint (median 1.0 vs 0.0 microg/g, P =. 004) but not at other timepoints. Area-under-the-curve analysis of FVL was used to quantify cumulative vedolizumab stool loss. This demonstrated significant differences between week 14 clinical responders and non-responders (44 microg/g/day, 95% CI: 0-128 vs 233 microg/g/day, 95% CI 0-1139, P <. 0001), as well as between endoscopic responders and non-responders (48 microg/g/day, 95% CI 0-142 vs 179 microg/g/day, 95% CI 0-142, P =. 0017), with non-responders having a higher rate of cumulative loss. Conclusions Active UC results in fecal loss of vedolizumab. This correlates with lower SVL and decreased response to treatment. Fecal loss of vedolizumab may be a marker of disease activity and/or result in lower rates of drug exposure at a tissue level, negatively impacting response.Copyright © 2025 The Author(s). Published by Oxford University Press on behalf of European Crohn's and Colitis Organisation. All rights reserved.