P1144 Effect of baseline disease severity on achieving efficacy endpoints in patients with Ulcerative Colitis treated with filgotinib
Authors: Allez M , Burisch J , Verstockt B , Dignass A , Fiorino G , Zabana Y , Saruta M , Sawyer W , Rudolph C , Vyncke V , Irving P 
Published: January 2025

Abstract

Background
Data from the real-world GALOCEAN study showed that ~70% of patients have moderately active Ulcerative Colitis (UC).1 A post hoc analysis of the SELECTION study (NCT02914522) found that patients with moderately active UC were more likely to have sustained responses to filgotinib (FIL) than those with severely active UC.2 We report outcomes for patients with moderate (MOD) versus severe (SEV) UC by Mayo endoscopic subscores (ES) in a post hoc analysis of SELECTION.

Methods
In the phase 2b/3, double-blind, placebo-controlled SELECTION study, 659 patients (18–75 years old) with moderately to severely active UC were randomized (2:2:1) at week 0 (W0) to daily oral FIL 200 mg (FIL200) or 100 mg, or placebo (PBO) for 11 weeks in Induction Study A (biologic [bio]-naive) or B (bio-experienced [bio-exp]).3 Patients with a clinical response at week 10 (W10) were re-randomized (2:1) to FIL or PBO maintenance treatment until week 58 (W58). MOD vs SEV active UC subgroups were defined as a Mayo ES of 2 or 3, respectively. Proportions of patients achieving efficacy endpoints (see Figure footnotes) were compared between subgroups for FIL200 and PBO.

Results
At W0, mean Mayo Clinic Scores (SD) for MOD versus SEV in bio-naive were 7.8 (1.1) versus 9.2 (1.1); for bio-exp, 7.9 (1.3) versus 9.6 (1.2). The proportion of patients with CRP ≥3mg/L was lower for MOD versus SEV (41% [46/112] vs 66% [88/133]). In the bio-naive, MOD subgroup, fewer patients had UC duration ≥7 years versus the SEV subgroup (35% vs 44%); the bio-exp MOD subgroup had a greater proportion of females versus the SEV subgroup (64% vs 37%). At W10 and W58, significantly greater achievement rates were observed for patients taking FIL200 versus PBO for most outcomes in both UC activity subgroups (greater for MOD than SEV), and for bio-naive and bio-exp patients (Figures 1 and 2). Achievement rates at W10 were greatest for FIL200-treated, bio-naive MOD patients (e.g. ES response for MOD vs SEV: 46% vs 24%). By W58, differences between severity subgroups were less pronounced in bio-naive patients (e.g. ES response: 59% vs 46%); differences between bio-exp subgroups were maintained.

Conclusion
These data show that patients with moderate or severe UC treated with FIL200 have improvements in efficacy outcomes and quality of life versus PBO; W10 outcomes were generally more favourable and sustained for the MOD subgroup, especially in bio-naive patients. Between-subgroup differences for bio-naive patients became less pronounced over time because response rates increased in the SEV subgroup up to W58. Analyses of the response dynamics for patients with moderate and severe UC activity by ES (and other definitions of UC severity) are ongoing.

References
1.Löwenberg M et al. United European Gastroenterol J 2024;12 Suppl 2:406–7.
2.Schreiber S et al. United European Gastroenterol J 2024; doi:10.1002/ueg2.12686.
3.Feagan BG et al. Lancet 2021;397:2372–84.