P0754 Extensive disease clearance as a novel composite endpoint to predict long-term relapse in vedolizumab-treated patients with ulcerative colitis: a post-hoc analysis from the VIEWS randomised controlled trial

Abstract

Background and Aim: Disease clearance (DC: clinical/endoscopic/ histologic remission) has been proposed as the ultimate therapeutic target in ulcerative colitis (UC). The effect of adding faecal calprotectin (FC) remission to DC, now proposed as «complete disease clearance» (CDC), in predicting relapses is unknown. We aimed to assess whether CDC better predicts long‐term outcomes than DC for UC patients on vedolizumab (VED). Methods: The Vedolizumab Immunomodulator Enforced Withdrawal Study (VIEWS) prospectively recruited UC patients in steroid‐free clinical remission on intravenous VED 300 mg q8w. Baseline assessments included FC, endoscopy and histology. Remission definitions were FC <150 μ g/g, centrally read Mayo endoscopic score (MES) = 0, and Nancy index (NI) = 0. FC value differentiated DC and CDC. DC was defined as MES=0, NI=0 and FC ≥150 μ g/g. CDC was defined as MES=0, NI=0 and FC <150 μ g/g. Clinical relapse (partial Mayo score ≥3 and FC ≥150 μ g/g or MES increase of ≥1) was evaluated over 24 months. Cox regression, Kaplan‐Meier curves and log rank statistics were performed to assess time to clinical relapse. Multivariate logistic regression was performed to identify predictive factors of relapse. Results: Among 62 patients followed over 24 months, baseline CDC was associated with significantly lower relapse rates compared with DC and clinical/endoscopic remission (log rank P<0.001; hazard ratio 0.17 [95% CI 0.04‐0.64], P=0.009) (Fig. 1). Baseline CDC had an odds ratio (OR) of 0.16 (95% CI 0.04‐0.75, P=0.01) in predicting relapse, versus DC (OR 0.20 [95% CI 0.05‐0.89], P=0.03), endoscopic remission (OR 0.91 [95% CI 0.16‐5.15], P=0.92), histologic remission (OR 0.10 [95% CI 0.02‐0.50], P=0.002), and neither endoscopic nor histologic remission (OR 4.44 [95% CI 0.55‐35.90], P=0.13). Female sex (P=0.03), disease duration <5 years (P=0.01), smoking status (P=0.004) and VED concentrations (P=0.03) were associated with CDC on univariate analysis. On multivariate analysis, only female sex (OR 7.0 [95% CI1.17‐42.33], P=0.03) predicted for CDC. Conclusion: CDC, a novel composite endpoint, predicted for significantly lower relapse rates compared with DC in UC patients on VED. Female sex was associated with baseline CDC. FC should be incorporated into composite endpoints with endoscopy and histology.