Treat-to-target optimization of biologic therapy is effective on endoscopic and histologic outcomes in a real-life cohort of ulcerative colitis-the TACTIC-UC study

Background & Aims: In ulcerative colitis (UC), therapeutic goals are evolving beyond symptom control toward endoscopic and histologic healing. However, optimal strategies to achieve these targets are undefined, and the implementation of treat-to-target (T2T) in patients with minimal symptoms despite ongoing intestinal inflammation remains unexplored. This study evaluated the real-world effectiveness of endoscopy-guided optimization in this population. Methods: TACTIC-UC is a retrospective, single-centre study including UC patients undergoing endoscopy-guided optimization of anti-TNF agents, vedolizumab, or ustekinumab. Eligible cases had quiescent or mild symptoms (partial Mayo score 0-4) but moderate-to-severe endoscopic activity (endoscopic Mayo Score, eMS >= 2) and underwent treatment optimization within 1 month after index endoscopy. The primary outcome was mucosal healing (MH, eMS <= 1) within 1 year. Secondary endpoints included endoscopic remission (ER, eMS = 0), histo-endoscopic mucosal remission (HEMR, eMS = 0 + Nancy Index = 0-1), biomarker trends, steroid use, adverse events, and treatment persistence. Results: A total of 164 optimization episodes were analysed in 142 patients. The 1-year cumulative probabilities of MH, ER, and HEMR were 54.2%, 28.8%, and 20.9%, respectively. In weighted analyses, anti-TNF-alpha therapies outperformed non-anti-TNF-alpha agents (vedolizumab and ustekinumab pooled together) across all outcomes: 66.3% versus 45.0% for MH, 39.3% versus 19.8% for ER, and 33.2% versus 8.1% for HEMR (all P-values < 0.05); consistent trends were confirmed in an exploratory 3-arm analysis incorporating synthetic data augmentation. Baseline steroid use and an eMS of 3 were independently associated with reduced probability of achieving endoscopic and histologic outcomes. No safety signals emerged. Endoscopic and histologic outcomes were associated with improved treatment persistence. Conclusions: In UC patients with quiescent or mild symptoms but active endoscopic inflammation, endoscopy-guided optimization of biologics is effective in achieving deeper inflammatory control, supporting its integration into T2T strategies.