DOP001 Endoscopic and histologic outcomes in patients with moderate-to-severe Ulcerative Colitis treated with infliximab: A post hoc analysis of the Phase 3 LIBERTY-UC study
Authors: Colombel J F , Hanauer S B , Schreiber S , Danese S , Deepak P , Horst S N , Jeong A L , Kim D H , Lee Y N , Sands B E 
Published: January 2025

Abstract

Background
The combined achievement of endoscopic and histologic remission is an emerging therapeutic target in ulcerative colitis (UC) and is associated with lower clinical relapse rates and reduced corticosteroid use.1,2 Here, we present endoscopic and histologic outcomes following maintenance treatment with subcutaneous (SC) infliximab (IFX) using data from the LIBERTY-UC study.3

Methods
In the LIBERTY-UC study,3 patients (pts) received induction doses of IFX 5 mg/kg via intravenous infusion at Weeks (W) 0, 2 and 6. Clinical responders at W10 were randomised 2:1 to receive either IFX SC every other week or a placebo (PBO) during maintenance therapy. All pts randomised at W10 were included in this post hoc analysis. Endoscopic and histologic assessments were performed at screening, W8, W22 and W54 (centrally evaluated). Endoscopic improvement (Mayo endoscopic subscore [MES] ≤1), endoscopic normalisation (MES=0), histologic remission (Robarts Histopathology Index [RHI] &lt;3 without neutrophils in the epithelium or lamina propria) and the combination of histologic remission and endoscopic normalisation were assessed. Non-responder imputation was used for pts who underwent dose adjustment or had missing data. Data were analysed descriptively with nominal p-values.

Results
Baseline characteristics were similar between IFX SC and PBO groups, with 48.6% and 53.5% of pts having severe disease (MES=3); and mean histologic activity (RHI) of 17.0 and 18.0, respectively (Table). At W8, half of the pts achieved endoscopic improvement in both groups (IFX SC: 53.1%; PBO: 50.0%). From W22 onwards, the difference in rates of endoscopic improvement between the two groups was statistically significant (50.7% vs 34.0%; p=0.0011) up to W54 (43.9% vs 22.2%; p&lt;0.0001). Similar findings were observed for histologic remission. Endoscopic normalisation rate in the IFX SC group increased with continued treatment (23.8% at W8, 26.9% at W22 and 32.7% at W54), while it declined in the PBO group (21.5% at W8, 18.8% at W22 and 11.1% at W54). Furthermore, a greater proportion of pts in the IFX SC group achieved combined histologic remission and endoscopic normalisation compared to the PBO group from W22 up to W54 (22.1% vs 16.7% at W22; p=0.2072; 27.9% vs 11.1% at W54; p&lt;0.0001) (Figure).

Conclusion
Maintenance treatment with IFX SC resulted in significantly greater improvements in endoscopic and histologic outcomes at W54 compared to PBO. Endoscopic improvements were observed as early as W8, along with enhancements in stringent endpoints such as endoscopic normalisation and the combined endpoint of histologic remission and endoscopic normalisation over time, supporting the sustained benefit of a maintenance therapy with IFX SC.

References
1. Yoon H, et al. Gastroenterology. 2020;159(4):1262-1257.e7.
2. Bryant RV, et al. Gut. 2016;65(3):408-414.
3. Hanauer SB, et al. Gastroenterology. 2024;167(5):919-933.