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

Background and Aims We conducted a prospective study (FAVOUR) of patients with UC commencing vedolizumab to investigate faecal vedolizumab loss and its impact on serum levels and treatment outcomes. Methods FAVOUR recruited patients with moderate-to-severe UC commencing vedolizumab. Faecal vedolizumab levels (FVL) were measured at days 1, 4, 7 and at weeks 2, 6 and 14. Trough serum vedolizumab levels (SVL) were measured at weeks 2, 6 and 14. Results 36 patients were recruited, of whom 33 completed induction therapy. Faecal 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 time point (median 1.0 vs 0.0ug/g, p = 0.004) 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 ug/g/day, 95% CI: 0-128 vs 233 ug/g/day, 95% CI 0-1139, p < 0.0001), as well as between endoscopic responders and non-responders (48 ug/g/day, 95% CI 0-142 vs 179 ug/g/day, 95% CI 0-142, p = 0.0017), with non-responders having a higher rate of cumulative loss. Conclusions Active UC results in faecal loss of vedolizumab. This correlates with lower SVL and decreased response to treatment. Faecal 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.