DOP21 Histo-endoscopic remission (HEMR) Predicts Future Relapse in Patients with Ulcerative Colitis and is Associated with Lower Colectomy Risk

Abstract

Abstract Background Treating beyond clinical and endoscopic remission, aiming for histological remission, is an aspiring target in ulcerative colitis [UC]. Hence, combined histo-endoscopic endpoints are increasingly being embraced. We assessed different degrees of histologic remission in patients with UC and their association with long-term outcomes. Methods UC patients achieving endoscopic improvement (Mayo endoscopic score [MES] ≤1) were recruited at colonoscopy. Clinical data were retrospectively collected from medical records. Endoscopies were video-recorded and biopsies from the most affected segment were collected for histological assessment and RNAseq (in case of MES 0 rectosigmoid biopsies were collected according to previous disease extent). Geboes Score [GS] and Robarts Histopathology Index [RHI] were determined for each biopsy by two pathologists blinded to the endoscopic scores. Non-histo-endoscopic remission [NHR], histo-endoscopic mucosal remission [HEMR] and histo-endoscopic mucosal normalization [HEMN] were defined as GS ≥2B.1, GS <2B.1 and GS ≤0.1. Clinical relapse was defined as the need for dose optimization, switching therapy or initiation of corticosteroids during follow-up. Long-term outcomes were analysed using log-rank test and Cox regression. Results Between 2016 and 2022, a total of 172 UC patients were included (Table). Endoscopic remission (MES 0) was achieved in 104 (60.4%) patients. NHR, HEMR and HEMN were observed in 15 (14.4%), 69 (85.6%), 51 (49.0%) of MES 0 patients and 32 (47.1%), 36 (52.9%), 18 (26.5%) of MES 1 patients. During a median [IQR] follow-up of 2.8 (1.9-3.9) years, 51 (29.7%) patients relapsed, and 7 (4.0%) patients needed colectomy. Relapse- and colectomy-free survival (Figure) were significantly higher when comparing HEMR to NHR (p<0.001 for both). This difference was not observed for endoscopic score (MES 0 vs. 1) or different degrees of histologic remission (HEMN vs. HEMR). The univariate Cox regression showed that histo-endoscopic activity, clinical activity (i.e., patient reported outcomes (PRO-2) for stool frequency or rectal bleeding > 0) and prior advanced therapy failure were associated with an increased risk of relapse. The multivariate Cox regression identified histo-endoscopic activity as the only risk factor for relapse (adjusted hazard ratio [HR]) = 3.01, 95% confidence interval [1.69-5.34], p<0.001). Conclusion In this cohort of UC patients with endoscopic improvement, 14.4% of MES 0 and 47.1% of MES 1 patients still showed signs of histologic activity (i.e., presence of neutrophils in the lamina propria or epithelium. Histologic remission was a superior predictor of future outcome (relapse, colectomy) when compared to endoscopic remission and showed to be the sole predictor of relapse.