Influence of drug exposure on vedolizumab-induced endoscopic remission in anti-TNF naïve and anti-TNF exposed IBD patients.

Background and Objectives: Vedolizumab has demonstrated efficacy and safety in patients with Crohn's disease [CD] and ulcerative colitis [UC]. Endoscopic outcome data are limited, especially in anti-tumour necrosis factor [TNF] naive patients.The present study compared endoscopic outcome in anti-TNF naive and exposed patients, and explored if this was affected by drug exposure. Methods: We retrospectively analysed all patients initiating vedolizumab at our tertiary referral centre since 2015. For UC, endoscopic improvement was defined as a Mayo endoscopic subscore <= 1 at week 14. For CD, endoscopic remission was defined as absence of ulcerations at week 22. Vedolizumab trough concentrations were measured at week 6, week 14 and during maintenance. Results: A total of 336 patients were identified [53.3% CD], 20% of them being anti-TNF naive. Endoscopic improvement was achieved by 56.1% of UC patients and endoscopic remission by 39.1% of CD patients. Endoscopic outcomes were significantly better in anti-TNF naive vs exposed patients [all: 67.2% vs 42.0%, p= 0.0002; UC: 74.4% vs 50.0%, p = 0.02; CD: 57.1% vs 35.8%, p= 0.03]. Achievement of endoscopic end points significantly impacted long-term treatment continuation [p = 9.7 x 10(-13)]. A better endoscopic outcome was associated with significantly higher drug exposure in both CD and UC. Conclusions: The results of this observational, single-centre real-life study suggest that vedolizumab may induce endoscopic remission in both CD and UC. Although anti-TNF naive patients had a significantly better outcome, 42% of anti-TNF exposed patients still benefited endoscopically. A clear exposure-endoscopic response relationship exists, but not all patients will benefit from treatment intensification. Hence, predictive biomarkers remain necessary.