P816 Baseline disease severity of patients with Ulcerative Colitis influences rapid symptom relief under filgotinib treatment: post hoc analysis of the phase 2b/3 SELECTION study

Abstract

Background: Filgotinib (FIL) is an oral, once‐daily, Janus kinase 1 preferential inhibitor approved in Europe and Japan for the treatment of ulcerative colitis (UC). A recent analysis of SELECTION trial data (NCT02914522) showed rapid and sustained improvements in UC symptoms with FIL 200 mg (FIL200) treatment in patients with moderate‐to‐severe UC.1 Here we assess symptomatic remission rates over time with FIL200 induction treatment according to baseline UC disease severity (partial Mayo Clinic Score [pMCS]). Methods: SELECTION was a phase 2b/3 randomized, double‐blind, placebo‐controlled study. Patients aged 18‐75 years were randomized (2:2:1) to receive FIL200, FIL 100 mg or placebo once daily for 11 weeks in induction study A (biologic‐naive patients) or induction study B (biologicexperienced patients). In this post hoc analysis, proportions of patients with symptomatic remission (Mayo rectal bleeding sub‐score of 0 and Mayo stool frequency sub‐score of ≤ 1), from days 2 to 15 and weeks 2 to 10 of the induction study, were analysed at each timepoint by baseline pMCS (pMCS ≥7 and pMCS <7 [cut‐off previously used for severe and moderate disease, respectively]2). Symptomatic remission rates were compared between the pMCS ≥7 and pMCS <7 groups within the FIL200 and placebo arms using a Cochran‐Mantel‐Haenszel test adjusted by study randomization stratification factors. Nominal p values <0.05 were considered statistically significant. Results: At day 2, symptomatic remission rates with FIL200 treatment were significantly higher in patients with baseline pMCS <7 than in those with baseline pMCS ≥7 (8.4% vs 1.1%, p=0.009 [induction study A]; 8.8% vs 0.7%, p=0.004 [induction study B]) (Figure A and B). From days 2 to 15, symptomatic remission rates increased in both groups and, except for day 7 for induction study A and day 9 for induction study B, continued to be significantly higher in those with baseline pMCS <7. From week 2, symptomatic remission rates with FIL200 treatment generally continued to increase in both pMCS ≥7 and pMCS <7 groups (Figure C and D). By week 10, symptomatic remission rates with FIL200 treatment were no longer significantly different between those with baseline pMCS <7 and those with baseline pMCS ≥7 (54.8% vs 43.3%, p=0.124 [induction study A]; 39.5% vs 26.4%, p=0.099 [induction study B]). Conclusion: Symptomatic response to FIL200 occurs more rapidly in patients with lower UC disease severity than in those with higher UC disease severity. However, converging response rates over 10 weeks of treatment leads to symptomatic remission regardless of baseline UC disease severity. (Figure Presented).