Hierarchical benefit of multidimensional remission in ulcerative colitis: a systematic review and meta-analysis

Current treat-to-target strategies for ulcerative colitis (UC) prioritize clinical remission (CR) and endoscopic remission (ER). However, whether achieving deeper remission (histologic remission [HR] or biochemical remission [BR]) confers incremental and sustained benefit beyond CR-ER endpoints remains unquantified. This study aimed to provide evidence supporting the hierarchical benefit of multidimensional remission on critical outcomes in UC. We systematically searched Medline, EMBASE, and Cochrane CENTRAL from inception to 19 May 2025 for cohort studies enrolling adults with UC in CR, with ≥ 6 months of follow-up, comparing relapse risk, corticosteroid reintroduction, hospitalization, colectomy, and colorectal cancer rates among patients achieving ER versus non-ER, HR versus non-HR, and/or BR versus non-BR. Data were synthesized using random-effects meta-analysis. The certainty of evidence was evaluated with GRADE. 94 studies (12,634 patients) were included. Compared to non-ER, ER reduced relapse risk by 44%–72% between 6 to < 60 months and corticosteroid reintroduction risk by 70% at 12 months (relative risks [RR] 0.30 [95% CI, 0.10–0.90]; very low certainty). Adding HR to CR + ER further reduced relapse risk by 51%–72% across all follow-up intervals: 12–24 months (0.46 [0.34–0.62]; moderate certainty), 24–36 months (0.48 [0.36–0.64]; moderate certainty), 48–60 months (0.28 [0.16–0.51]; low certainty), and ≥ 60 months (0.49 [0.34–0.71]; low certainty). Adding BR to CR + ER provided additional risk reduction of 71% at 12-month (0.29 [0.16–0.50]); moderate certainty), and 29% at ≥ 60 months (0.71 [0.51–0.97]; very low certainty). This meta-analysis suggests a hierarchical benefit of multidimensional remission in UC. Achieving HR or BR beyond CR-ER endpoints substantially and sustainably reduces relapse risk. These results suggest that HR and BR may be considered as potential treatment targets to optimize long-term disease control.