S1451 Efficacy and Safety Profile of Etrasimod Was Not Impacted by Baseline Disease Activity: A Post Hoc Analysis of the ELEVATE UC Program
Bibliographic record
Abstract
Introduction: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Methods: In this post hoc analysis of ELEVATE UC 52 (NCT03945188; treat-through design with 12-week [wk] induction then 40-wk maintenance periods) and ELEVATE UC 12 (NCT03996369; 12-wk induction period), etrasimod efficacy and safety were assessed according to baseline (BL) disease activity. Patients (pts) aged 16–80 years with moderately to severely active UC were randomized 2:1 to etrasimod 2 mg once daily or placebo (PBO).1 Pts’ BL UC activity was stratified as moderately or severely active based on a modified Mayo score (MMS) of 5–7 or 8–9, respectively. Efficacy endpoints including mean percentage change from BL in MMS and clinical response/remission per MMS category were measured at Wk12. Pooled efficacy data were analyzed descriptively; 95% confidence intervals (CIs) were calculated for all means or proportions with normal approximation or simultaneous estimation method, respectively. Safety was assessed up to Wk52 in the pooled safety analysis set. Results: Of the 743 pts in this analysis, 525 (70.7%) and 218 (29.3%) had a BL MMS of 5–7 and 8–9, respectively. BL characteristics were broadly similar across subgroups, except for lower rates of proctitis in pts with MMS 8–9 vs 5–7 (3.3% and 3.0% vs 9.3% and 9.4% in etrasimod and PBO groups, respectively; Table 1). At Wk12, pts taking etrasimod had larger mean percentage reductions (95% CI) in MMS vs PBO, regardless of BL disease activity (48.4% [52.3, 44.4] vs 27.0% [32.2, 21.7] for BL MMS 5–7, and 46.4% [51.2, 41.5] vs 29.8% [37.2, 22.3] for BL MMS 8–9). At Wk12, more pts taking etrasimod achieved clinical response vs PBO, regardless of BL disease activity, with an overall reduction from BL disease activity as measured by MMS categorization in both BL MMS subgroups (Figure 1). Proportions of pts with treatment-emergent adverse events (TEAEs) were broadly similar across treatment and BL disease activity subgroups (any TEAE: 59.0% vs 50.8% and 65.1% vs 56.1% for etrasimod vs PBO, in BL MMS 5–7 and 8–9 groups, respectively). Conclusion: Etrasimod showed greater reductions in disease severity and higher rates of clinical response, vs PBO, regardless of BL disease activity. Its safety profile was consistent with the overall trial population1 and was not impacted by BL disease activity. Reference: 1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171.Figure 1.: Proportion of pts achieving clinical response in each MMS category at Wk12 stratified according to baseline disease activity (pooled data from ELEVATE UC 52 and ELEVATE UC 12). [a]Clinical response was defined as a ≥ 2-point and ≥ 30% decrease from baseline in MMS, and a ≥ 1-point decrease from baseline in RBS, or RBS ≤ 1. [b]MMS was not available for some pts at Wk12 for various reasons, including discontinuation prior to Wk12. Data were pooled from ELEVATE UC 52 and ELEVATE UC 12. MMS, modified Mayo score; pt, patient; RBS, rectal bleeding subscore; UC, ulcerative colitis; Wk, Week. Table 1. - Demographics and baseline characteristics of patients in the ELEVATE UC clinical program[a] stratified according to baseline disease activity Baseline MMS 5–7 (moderate) Baseline MMS 8–9 (severe) Placebo QD(N = 181) Etrasimod2 mg QD(N = 344) Placebo QD(N = 66) Etrasimod2 mg QD(N = 152) Age (years), mean (SD)Female, n (%)Race, n (%)WhiteAsianBlack or African AmericanOtherDuration of UC (years), mean (SD)Proctitis,b n (%)Baseline MMS, mean ES of 3 at baseline, n (%)Baseline CS use, n (%)Naïve to biologic/JAKi, n (%) 40.3 (13.9)70 (38.7)154 (85.1)21 (11.6)2 (1.1)4 (2.2)7.0 (6.7)17 (9.4)6.3 86 (47.5)53 (29.3)126 (69.6) 40.6 (13.9)158 (45.9)278 (80.8)45 (13.1)7 (2.0)14 (4.1)7.5 (7.5)32 (9.3)6.3 144 (41.9)89 (25.9)240 (69.8) 37.6 (12.9)27 (40.9)53 (80.3)10 (15.2)3 (4.5)06.4 (6.1)2 (3.0)8.1 62 (93.9)19 (28.8)41 (62.1) 42.2 (13.8)69 (45.4)132 (86.8)16 (10.5)1 (0.7)3 (2.0)7.3 (7.1)5 (3.3)8.1 145 (95.4)58 (38.2)102 (67.1) aPooled for ELEVATE UC 52 and ELEVATE UC 12.bCentral read.CS, corticosteroid; ES, endoscopic subscore; JAKi, Janus kinase inhibitor; MMS, modified Mayo score; N, number of patients in the baseline disease activity subgroup by treatment; n, number of patients in the specified category; QD, once daily; SD, standard deviation; UC, ulcerative colitis.
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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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| 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".