Introduction

The STRIDE-2 consensus emphasizes achieving specific endoscopic targets in ulcerative colitis (UC), but robust evidence on the effectiveness of the Treat-to-Target (T2T) approach in UC is limited in the real-world setting.

Aims & Methods

TACTIC-UC is a monocentric, retrospective, observational study evaluating UC patients managed according to a T2T algorithm. Eligible patients: 1) were receiving anti-TNF (aTNF), vedolizumab (VDZ) or ustekinumab (UST) at standard doses, 2) had quiescent/mild clinical activity (stool frequency and rectal bleeding <1), 3) had moderate/severe endoscopic activity (endoscopic Mayo score, eMS≥2). All patients received dose optimization and had at least 1 follow-up endoscopy. Observation period lasted from optimization until 1 year /drug discontinuation/last available follow-up. The primary outcome was the probability of mucosal healing (MH, eMS≤1) within 1 year. Secondary outcomes included: 1) probability of endoscopic remission (ER, eMS=0) within 1 year, 2) adverse events (AEs) incidence. Inverse probability of treatment weighting was used to adjust cohorts’ imbalances. False discovery rate correction was applied for multiple comparisons.

Results

The cohort included 178 patients (main characteristics in Table 1); after IPTW, no significant differences were observed. The cumulative probabilities of achieving MH within the first year were 41%, 11% and 23% for aTNF, VDZ and UST, respectively. At pair-wise comparison, aTNF was superior to both VDZ and UST(p<.05), with UST trending towards superiority (p=.05) over VDZ. Cox-regression (bootstrapping, 1000 iterations) identified factors associated with a significantly reduced (p<.05) probability of achieving MH: difficult-to-treat UC (aHR 0.6, 95%CI 0.5-0.7), E3 (aHR 0.7, 95%CI 0.5-0.9), elevated CRP (aHR0.96, 95%CI 0.94-0.9), and elevated FCP (aHR 0.98, 95%CI 0.97-0.99); aTNF was associated with increased probability of MH compared to VDZ (aHR 1.4, 95%CI 1.1-1.7, p<.05) and UST (aHR 1.4, 95%CI 1.2-2.0, p<.05). For ER, the cumulative probabilities at 1 year were 13%, 3% and 9% for aTNF, VDZ and UST, respectively. Pairwise comparisons showed that aTNF was superior to VDZ (p<.05), and UST trended towards superiority over VDZ (p=.05). Cox regression (bootstrapping, 1000 iterations) found that difficult-to-treat UC (aHR 0.6, 95%CI 0.5-0-8), E3 (aHR 0.7, 95%CI 0.6-0.), higher CRP (aHR 0.97, 95% CI 0.95-0.99), higher FCP (aHR 0.99, 95%CI 0.98-1.0) were significantly (p<.05) associated with reduced probability of achieving ER; aTNF was associated with increased probability of achieving ER compared to VDZ (aHR 1.3, 95%CI 1.1-1.7, p<.05) and UST (aHR 1.4, 95%CI 1.1-2.0, p<.05), with no significant difference for VDZ vs UST. AEs were infrequent and mild across all groups (mostly infections and infusion reactions), with no significant differences in safety profiles. No serious AE was reported.
Table 1.

Conclusion

In this cohort of UC patients treated according to an endoscopy-driven T2T approach, aTNF outperformed VDZ and UST in inducing MH and ER. Disease severity markers were associated with reduced probabilities of achieving endoscopic targets. Safety profiles were comparable across therapies.