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
Authors: Pudipeddi A , Lin H , Paramsothy S , Kariyawasam V , Paramsothy R , Ghaly S , Haifer C , An Y K , Begun J , Connor S , Corte C , Ward M , De Cruz P , Fung C , Redmond D , Chan W , Mourad F , Kermeen M , Leong R 
Published: January 2025

Abstract

Background
Disease clearance (DC), defined as combined clinical, endoscopic and histologic remission, has been proposed as the ultimate therapeutic target in ulcerative colitis (UC). However, the addition of faecal calprotectin (FC) remission to DC, now proposed as ‘extensive disease clearance (EDC)’, in predicting for relapse is unknown. We aimed to explore the use of composite therapeutic endpoints, including DC and EDC, in predicting long-term outcomes for UC patients on vedolizumab (VED).

Methods
The phase IV Vedolizumab Immunomodulator Enforced Withdrawal Study (VIEWS) prospectively recruited UC patients in steroid-free clinical remission on VED 300mg IV q8w. Baseline evaluation (week 0) included FC, endoscopy, histology and serum VED trough levels. Remission definitions were FC&lt;150µg/g, centrally-read Mayo endoscopic score (MES)=0 and Nancy index (NI)=0. FC value differentiated DC and EDC. DC was defined as FC≥150µg/g, MES=0 and NI=0. EDC was defined as FC&lt;150µg/g, MES=0 and NI=0. Clinical relapse, defined as partial Mayo score ≥3 and FC≥150µg/g or MES increase of ≥1, was evaluated for 2 years. Cox regression, Kaplan-Meier curves and log rank statistics were performed to assess the time to clinical relapse. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for dichotomous categorial variables. Multivariate logistic regression models were performed to identify predictive factors of relapse. P&lt;0.05 was deemed statistically significant (SPSS, IBM, USA).

Results
62 consecutively recruited UC patients were followed over 24 months. Of 54 patients with endoscopic assessments at baseline, 80% were in endoscopic remission, 76% histologic remission, 68% had DC, and 63% had EDC. Baseline EDC was associated with significantly lower rates of clinical relapse compared with DC and clinical/endoscopic remission alone (log rank P&lt;0.001; HR: 0.17 [95%CI:0.04-0.64], P=0.009) (Figure 1). Baseline EDC had an 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). Univariate predictors of EDC at baseline were female sex (P=0.03), UC disease duration &lt; 5 years (P=0.01), smoking status (P=0.004) and serum VED concentrations (P=0.03). On multivariate analysis, only female sex (OR: 7.0 [95%CI: 1.17-42.33], P=0.03) predicted for EDC.

Conclusion
EDC, a novel composite endpoint, predicted for significantly lower rates of relapse compared with DC in UC patients on VED. Female sex was associated with baseline EDC. FC should be incorporated into composite endpoints with endoscopy and histology.