Disease Clearance in Ulcerative Colitis: a Multicenter Survival Analysis of Long-term Outcomes in Patients Receiving Advanced Therapies

Background: Therapeutic targets for ulcerative colitis (UC) are rapidly evolving. The STRIDE-2 consensus established endoscopic remission as the long-term goal, as it reduces negative outcomes including clinical relapses, hospitalizations, and surgeries. Recently, the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) introduced Disease Clearance (DC), a composite outcome combining clinical, endoscopic, and histological remission that appears more predictive of reducing long-term negative outcomes compared to endoscopic remission alone. While biologic drugs and small molecules have demonstrated the ability to induce DC, it remains unclear which therapies are most effective in achieving this therapeutic goal. Objective: This multicenter study aimed to determine the percentage of UC patients achieving DC while undergoing advanced therapies at four Italian centers (Padova, Torino, Genova, Pisa), and to identify which advanced therapy is most effective in achieving DC. Methods: Adult patients with UC receiving advanced therapies from 2011 to 2025 with endoscopic and histological examinations before and after therapy initiation were enrolled. Patients with previous surgical resections were excluded. DC was defined as simultaneous clinical remission (partial Mayo Score = 0), endoscopic remission (endoscopic Mayo Score = 0), and histological remission (Geboes Score ≤ 1). Cox regression survival analysis was performed to evaluate the impact of DC on composite outcomes including disease flare, treatment interruption, and surgery. Results: Among 299 patients analyzed, DC was achieved by 26.7% during a median follow-up of 2.4 years (range: 67 patients achieved DC vs 232 who did not). Patients achieving DC were significantly younger at diagnosis (31.6 vs 37.8 years, p=0.018), had lower baseline partial Mayo scores (3.3 vs 4.2, p=0.026), and more frequently had active extraintestinal manifestations (70.1% vs 56.0%, p=0.038). Among advanced therapies, Tofacitinib (38.5%) and Golimumab (35.5%) demonstrated the highest DC rates, though differences were not statistically significant. Multivariable Cox regression analysis revealed that DC was independently associated with a 41% reduction in the hazard of composite negative outcomes (HR 0.59, 95% CI 0.39-0.89, p=0.011). Survival analysis showed significant differences between DC and non-DC groups for disease flare (58 vs 22 months, p<0.001), treatment change/interruption (87 vs 52 months, p<0.001), and all composite outcomes (p<0.001 for all). No baseline parameters were identified as significant predictors of achieving DC. Conclusions: Although DC represents a therapeutic goal capable of significantly reducing long-term negative outcomes with a 41% hazard reduction, it is achieved in a relatively low percentage of UC patients (26.7%). No significant differences in efficacy were observed between advanced therapies, nor were baseline clinical parameters found to predict DC achievement.