Long-Term Clinical Outcomes of Ulcerative Colitis with Concurrent Endoscopic and Histologic Remission

Background and Objectives: Therapeutic goals for ulcerative colitis (UC) have expanded beyond symptom control to include mucosal and histological healing. However, the long-term prognostic value of achieving both targets remains uncertain, particularly in Asian populations. This study aimed to evaluate long-term outcomes and relapse predictors in patients with UC who achieved both endoscopic and histologic remission. Materials and Methods: This prospective observational study consecutively enrolled adults with clinically inactive UC who attained endoscopic remission (Mayo endoscopic subscore = 0) and histologic remission (Nancy index ≤1) between June 2014 and May 2018. Demographic, clinical, and laboratory data-including fecal calprotectin-were collected. Clinical relapse was defined as a Mayo score increase >3 or initiation of systemic corticosteroids or biologics. Patients were followed longitudinally for a median of 55 months (minimum 12 months), and relapse risk was evaluated using Kaplan-Meier and univariate Cox regression analyses. Results: A total of 41 patients were included (mean age 54 ± 14 years; 56% male). The median follow-up was 54 months (range 17-78). Ten patients (24.4%) relapsed during follow-up, with cumulative relapse rates of 9.8%, 10.3%, 15.8%, and 24.1% at 12, 24, 36, and 48 months, respectively. Kaplan-Meier analyses demonstrated significantly higher relapse in patients with non-E1 disease (E2 + E3, p = 0.021), immunomodulator use (p = 0.008), and biologics use (p = 0.007). In univariate Cox regression, immunomodulator (HR 4.7, 95% CI 1.3-16.4, p = 0.02) and biologics use (HR 4.9, 95% CI 1.4-17.5, p = 0.01) were significant predictors of relapse, whereas disease extent showed only a non-significant trend with wide CIs. Baseline fecal calprotectin was higher in the relapse group (182 ± 370 μg/g vs. 108 ± 164 μg/g) but was not statistically significant. Conclusions: Approximately one-quarter of UC patients who achieved dual remission relapsed within 4 years. These findings highlight the limitations of using dual remission as the sole therapeutic endpoint and underscore the need for additional prognostic factors. High-risk subgroups-such as those with extensive disease or prior exposure to advanced therapies-may require closer monitoring and individualized strategies. Future multicenter studies integrating clinical, endoscopic, histologic, and biomarker data are needed to refine relapse prediction.