P468 Etrolizumab treatment improves histological activity as assessed by the Robarts histopathology index
Bibliographic record
Abstract
Background: Etrolizumab, an anti-β7 mAb targeting α4β7 and αEβ7 integrins, showed efficacy and safety vs placebo (PBO) during 10 weeks of induction in patients with moderate-to-severe UC in the phase 2 trial, EUCALYPTUS. Because a reduction in histological inflammation has been linked with improved long-term clinical outcome (Bryant et al. Gut 2016), and the FDA recommends using both histological assessments and endoscopy to evaluate efficacy, we assessed the effect of etrolizumab on histological inflammation in mucosal biopsies from EUCALYPTUS patients using the Robarts histopathology index (RHI). Methods: Patients were randomly assigned (1:1:1) to subcutaneous etrolizumab (100 mg at weeks 0, 4 and 8, with PBO at week 2, or 420-mg loading dose at week 0, followed by 300 mg at weeks 2, 4 and 8), or matching PBO. Biopsies were taken using flexible sigmoidoscopy/full colonoscopy from the most inflamed colonic area within 10–40 cm from the anal verge at baseline (BL) and at week 10. Batched H&E stained slides were scored by a single pathologist using the Geboes scale and converted to RHI (Mosli et al. Gut 2015). At week 10, mean change from BL RHI score and mean difference between pooled etrolizumab and PBO were calculated. Subanalyses explored histological improvement (defined as categorical reductions in RHI of ≥6 points or ≥50% improvement from BL RHI score) and the relationship with endoscopic improvement. Results: Analysis included 89 (of 119 efficacy-evaluable) patients with BL histological data and BL RHI >1. Mean week 10 RHI reduction was greater for etrolizumab- compared with PBO-treated patients regardless of previous aTNF experience, and a greater proportion of patients receiving etrolizumab achieved histological improvement compared with PBO. Of patients with an endoscopic subscore (ES) ≤1 at week 10, 89% experienced histological improvement. Mean (SD) RHI change was −14.2 (5.5) in patients with an ES ≤1 at week 10 versus −2.5 (9.5) in patients with an ES >1. Table 1 Figure 1 Conclusions: RHI-measured histological activity improved after 10 weeks of etrolizumab treatment. Consistent with the clinical remission rates observed in EUCALYPTUS, the magnitude of histological improvement was greater in the aTNF-naive vs aTNF-IR subgroup. RHI reductions are associated with improved ES at week 10.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".