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DOI: 10.1055/s-0045-1810744
Symptomatic response trajectories of etrasimod in UC patients: a post hoc analysis of the ELEVATE UC 52 trial
Authors
Introduction: Identifying patient (pt) populations and long-term treatment response factors can enable personalised management strategies in ulcerative colitis (UC). Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC.
Objectives: To identify subgroups with distinct response trajectories based on changes in combined rectal bleeding subscore (RBS) and stool frequency subscore (SFS) over time.
Methodology: This post hoc analysis of etrasimod-treated pts from ELEVATE UC 52 used pt-reported outcome 2 (PRO2; RBS+SFS) to identify response trajectories and assess Week (Wk) 52 endpoint achievement. A composite of objective and subjective disease activity measures, previously used in trajectory modelling, was assessed as comprehensive disease control (CDC). CDC was defined by Wk 52 criteria: complete treatment (Wk 50), clinical remission, RBS and SFS=0, endoscopic subscore=0/1, complete Mayo score≤2, histological remission (Geboes score<2 or Robarts Histopathology Index<3) and C-reactive protein and/or faecal calprotectin in normal range. Longitudinal k-means analysed PRO2 disease activity data as individual time-series connected datasets. Response trajectory groups (TGs) were related to maintenance outcomes and baseline characteristics. Clinical relevance of this grouping was assessed by the proportions of pts achieving key endpoints and their association with baseline demographics.
Results: In 283 etrasimod-treated pts with UC, five TGs were identified ([Fig. 1]). 57% of super responders achieving CDC were clustered in TGs C and E, characterised by rapid response and sustained clinical remission (C: 34/51, E: 25/44), with lower baseline disease activity per histology and Mayo score components. In TGs B and D, 31.7% and 34% achieved clinical remission and 48.3% (29/60) and 53.2% (25/47) achieved clinical response. In TG E, symptomatic improvement per PRO2 continued beyond Wk 12.


Conclusion: Trajectory modelling identifies phenotypic subgroups in pts with UC responding to targeted therapy, revealing heterogeneity often masked in single population analyses. Notably, some etrasimod-treated pts had super-fast and fast response dynamics, linked with higher clinical remission and CDC rates. This may provide utility for therapeutic choice and pt management. Further studies across therapies are ongoing to validate results and identify cross-population treatment effects.
Publikationsverlauf
Artikel online veröffentlicht:
04. September 2025
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