Abstract Background In ulcerative colitis (UC), therapeutic goals are shifting beyond symptom control toward endoscopic and histologic healing. Yet, optimal strategies to achieve these targets remain undefined, and the implementation of treat-to-target (T2T) in patients with minimal or no symptoms despite active inflammation is largely unexplored. This study assessed the real-world effectiveness of endoscopy-guided treatment optimization in this setting. Methods TACTIC-UC was a single-center, retrospective study including UC patients who underwent endoscopy-guided optimization of biologic therapy. Eligible patients had quiescent or mild symptoms (partial Mayo score ≤4 and rectal bleeding subscore ≤1) but moderate-to-severe endoscopic activity and underwent optimization within 1 month after the index endoscopy. The primary outcome was mucosal healing (MH, endoscopic Mayo score eMS ≤1) within 1 year. Secondary outcomes included endoscopic remission (ER, eMS=0), histo-endoscopic mucosal remission (HEMR, eMS=0 and Nancy Index=0–1), treatment persistence, and adverse events. Results A total of 164 optimization episodes (47.6% anti-TNF, 15.9% vedolizumab, 36.6% ustekinumab) were analyzed in 142 patients receiving biologics. At baseline, 49.4% had severe endoscopic activity, 29.9% were on corticosteroids, and 42.1% were naïve to advanced therapies. Optimization occurred after a median of 4.8 (IQR 3.3–8.9) months of treatment. One-year cumulative probabilities of MH, ER, and HEMR were 54.2% (42.0–63.8%), 28.8% (16.6–39.2%), and 20.9% (8.2–31.1%), respectively. After inverse probability of treatment weighting, anti-TNF therapies achieved significantly higher rates of all efficacy outcomes compared with vedolizumab and ustekinumab combined (Figure 1, p0.05 for all pairwise comparisons after multiplicity adjustment). Exploratory three-arm analyses incorporating synthetic data augmentation confirmed consistent trends: outcomes were highest with anti-TNF agents, intermediate with ustekinumab, and lowest with vedolizumab. Baseline corticosteroid use and severe endoscopic activity (eMS=3) independently predicted lower likelihood of achieving endoscopic and histologic outcomes. Achieving endoscopic or histologic targets was associated with greater treatment persistence. No new safety concerns emerged. Conclusion In UC patients with mild or quiescent symptoms but active endoscopic inflammation, endoscopy-guided optimization of biologic therapy effectively promotes deeper inflammatory control, supporting its inclusion within T2T strategies. Patients with moderate endoscopic activity, not on corticosteroids, and receiving anti-TNF agents appear most likely to benefit from this proactive approach. Conflict of interest: Privitera, Giuseppe: Consultant fee from Johnson & Johnson Bezzio, Cristina: Personal Fees: I received consulting/advisory board/lecture fees from Alfa Sigma, AbbVie, Celltrion, Eli Lilly, Ferring, Gilead, Johnson & Johnson MSD, Pfizer and Takeda Dal Buono, Arianna: speaker’s fees from AbbVie, Alphasigma, Ferring, Lilly, Janssen, and Celltrion Gabbiadini, Roberto: No conflict of interest Laura, Loy: No conflict of interest Ranucci, Luca: No conflict of interest Bertin, Luisa: No conflict of interest Masoni, Benedetta: No conflict of interest Migliorisi, Giulia: No conflict of interest Sauta, Elisabetta: No conflict of interest Dellani, Mattia: No conflict of interest Savevski, Victor: No conflict of interest Della Porta, Matteo: No conflict of interest D’Amico, Saverio: No conflict of interest Armuzzi, Alessandro: Consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda
Privitera et al. (Thu,) studied this question.