S1145 Corticosteroid-Free Efficacy Outcomes in Patients Receiving Concomitant Corticosteroids at Baseline in the Etrasimod ELEVATE UC 52 Trial
Bibliographic record
Abstract
Introduction: Etrasimod is an investigational, oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). In ELEVATE UC 52 (NCT03945188), etrasimod was superior to placebo (PBO) in achieving Week (Wk) 52 corticosteroid (CS)-free clinical remission (CR).1 Methods: This post hoc analysis reports CS-free efficacy and safety in patients (pts) on baseline (BL) CS. Pts were randomized 2:1 to once-daily etrasimod 2 mg or PBO using a treat-through design (12-wk induction and 40-wk maintenance period). At entry, pts could receive concomitant CS (prednisone [≤ 20 mg/day], budesonide [≤ 9 mg/day] or equivalent) if on a stable dose ≥ 4 wks immediately before screening endoscopy; from Wk 12, CS tapering was recommended. CS-free was defined as withdrawal of CS ≥ 12 wks prior to assessment timepoint. CS-free outcomes assessed were CS-free CR at Wk 52, CS-free endoscopic improvement (EI) at Wk 52, and CR at Wk 12 + CS-free CR at Wk 52. From Wk 12, 4-wk CS-free symptomatic remission (SR; 4 wk in contrast to ≥ 12-wks CS free) was analyzed at each visit. Logistic regressions examined associations with CS-free efficacy at Wk 52. Safety was assessed. Results: At BL, 32.2% (93/289) and 29.2% (42/144) of etrasimod and PBO pts received CS; of these, significantly more etrasimod vs PBO pts achieved CS-free CR at Wk 52, CS-free EI at Wk 52 and CR at Wk 12 + CS-free CR at Wk 52 (all P < 0.05; Table 1). At Wks 40–52, there were significant differences (16.6–26.6%; P < 0.05) in 4-wk CS-free SR between etrasimod and PBO. In this subpopulation, being biologic/Janus kinase inhibitor-naïve was not a significant predictor of 12-wk CS-free CR at Wk 52 (odds ratio [OR]: 3.61; 95% confidence interval [CI] 0.91, 14.39; P=0.07); age, per 10-year increase, was significantly associated (OR: 1.51; 95% CI 1.03, 2.22; P=0.04). Etrasimod vs PBO pts with concomitant CS at BL experienced slightly more adverse events (AEs; not exposure adjusted) (71.0% [66/93] vs 61.9% [26/42]) but fewer serious AEs (6.5% [6/93] vs 14.3% [6/42]), including serious infections (0% [0/93] vs 7.1% [3/42]). Conclusion: More etrasimod vs PBO pts who received CS at BL met CS-free efficacy endpoints. Four-wk CS-free SR with etrasimod was superior to PBO from Wk 40. Concomitant CS use at BL had no notable negative effect on the safety of etrasimod, consistent with the overall ELEVATE UC 52 population. Reference: 1. Sandborn WJ et al. Lancet 2023; 401: 1159-1171.1 Table 1. - CS-Free Efficacy in Pts Receiving Concomitant CS at BL of ELEVATE UC 52 (FAS) Etrasimod 2 mg QD, n/N (%) PBO QD, n/N (%) Adjusted difference % (95% CI) p [a] 12-wk CS-free clinical remission at Wk 52 29/93 (31.2) 3/42 (7.1) 23.2 (10.6, 35.7)0.0003 12-wk CS-free endoscopic improvement at Wk 52 35/93 (37.6) 8/42 (19.0) 17.5 (2.5, 32.5)0.0226 CR at Wk 12 + CS-free CR at Wk 52 18/93 (19.4) 2/42 (4.8) 14.3 (3.5, 25.1)0.0092 All pts in the FAS had a modified Mayo score from 4 to 9 at BL. Clinical remission was defined as SFS=0 (or 1 with a ≥ 1-point decrease from BL), RBS=0 and ES ≤ 1 (excluding friability). Endoscopic improvement was defined as ES ≤ 1 (excluding friability).[a] Adjusted difference (%) is based on estimated common risk difference using Mantel-Haenszel weights; p is 2-sided to test the hypothesis of the adjusted risk difference being 0.BL, baseline; CR, clinical remission; CS, corticosteroid; ES, endoscopic subscore; FAS, full analysis set; n, number of unique pts achieving each endpoint; N, total number of pts in the analysis; PBO, placebo; pt, patient; QD, once daily; RBS, rectal bleeding subscore; SFS, stool frequency subscore; Wk, week.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".