P0828 The impact of etrasimod on neutrophils in the ELEVATE UC clinical programme
Bibliographic record
Abstract
Abstract Background Neutrophils are thought to play a role in the pathogenesis of ulcerative colitis (UC); they are believed to be the principal source of faecal calprotectin and are a histological marker of disease activity in mucosal biopsies. 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. This post hoc analysis evaluated neutrophils in patients (pts) receiving etrasimod or placebo (PBO) in the ELEVATE UC clinical programme. Methods We assessed percentage changes from baseline (BL) in absolute neutrophil counts (ANC) throughout ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369)1 for all pts and those who did or did not achieve clinical remission (clinical remitters) or endoscopic improvement-histologic remission (EIH remitters) at Week (Wk) 12. Transcriptional characterisation followed by cell type deconvolution analysis from bulk RNA-seq was performed on colonic biopsies to assess for neutrophils in clinical remitters vs nonremitters (at Wk 12). Incidence of neutropenia and potential associated infections were assessed. Results BL blood and colonic biopsy samples, respectively, were available for 432 and 340 pts (ELEVATE UC 52) and 353 and 249 pts (ELEVATE UC 12). Pts receiving etrasimod vs PBO had significant percent decreases from BL in ANC from Wk 4 (-14.9% vs -4.9%, p<0.05; ELEVATE UC 52) and Wk 2 (-12.0% vs 0.3%, p<0.05; ELEVATE UC 12); the greatest decrease was seen for pts receiving etrasimod at Wk 12 in ELEVATE UC 12 (-16.8%) and nadir was reached at Wk 20 in ELEVATE UC 52 (-24.5%) and maintained through Wk 52. Wk 12 clinical remitters vs nonremitters receiving etrasimod had significantly greater percent decrease in ANC from BL at most time points (p<0.05; Figure); a similar trend was seen for EIH remitters vs nonremitters. Colonic neutrophils were also significantly decreased at Wk 12 vs BL for pts receiving etrasimod (false discovery rate [FDR] <0.05) but not PBO, and for clinical remitters vs nonremitters receiving etrasimod (FDR <0.05). Across both trials, nine (etrasimod) and four (PBO) pts had neutrophil counts <1 × 109/L at any post-BL assessment. Of these pts, none reported subsequent serious, severe or opportunistic infections; one pt receiving etrasimod experienced a nonserious infection ≤60 days after reported neutropenia. Conclusion Our data support a relationship between decreased circulating and mucosal neutrophil levels and clinical and endoscopic improvement with etrasimod treatment in pts with UC, while showing a low likelihood of neutropenia. References 1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171. Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
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".