DOP03 Early change in epithelial neutrophilic infiltrate predicts long-term response to biologics in Ulcerative Colitis
Bibliographic record
Abstract
Abstract Background The prognostic value of histologic scores, grades, and individual histologic sub-components, alone or in combination with endoscopy, for predicting endoscopic improvement (EI) and histo-endoscopic mucosal improvement (HEMI) during maintenance therapy in ulcerative colitis (UC) remains uncertain. Methods Post-hoc analysis of participants from the VARSITY trial (n=734 with histology). Receiver operating characteristic and multi-variate logistic regression analyses were performed to assess whether baseline and/or week 14 assessments for the Robarts Histopathology Index (RHI), Geboes score, or individual histologic sub-components, could predict the achievement of EI and HEMI at week 52. Results RHI and Geboes scores at baseline, and changes in scores at week 14, had fair to poor accuracy for predicting week 52 EI or HEMI (Area Under the Curve [AUC] 0.58–0.67). Among individual sub-components, changes in epithelial neutrophil involvement from baseline to week 14 had the best performance for predicting week 52 EI (AUC 0.83, 95% confidence interval (CI) 0.74–0.91) and HEMI (AUC 0.85, 95% CI 0.76–0.94). On multivariate analyses, improvement of neutrophils in the epithelium was associated with increased odds of week 52 EI (Odds Ratio [OR] 3.63, 95% CI 1.45–9.08, p=0.0059) and HEMI (OR 6.88, 95% CI 3.29–14.36, p<0.0001), and lack of improvement of neutrophils in the epithelium was associated with lack of week 52 EI (OR 0.24, 95% CI 0.12–0.48, p<0.0001) and lack of HEMI (OR 0.03, 95% CI 0.01–0.014, p<0.0001). No other parameters significant on univariate analysis were significant within the multivariate model. Among patients with endoscopic Mayo scores of 2 or 3 at week 14, those who had >50% crypts involved with neutrophils at week 14 were significantly less likely to achieve week 52 EI (18.0%; 31/172 vs. 34.3%; 72/210, p<0.001), HEMI (9.9%; 17/172 vs. 22.4%; 47/210, p=0.001) (Figure 1) and clinical remission (11.0%; 19/172 vs. 23.3%; 49/210, p=0.002). Among patients with endoscopic Mayo scores of 0 or 1 at week 14, those who had >50% crypts involved with neutrophils were significantly less likely to achieve HEMI at week 52 (33%; 4/12 vs. 62.4%; 141/226, p=0.044) (Figure 1). Conclusion Our results on epithelial neutrophilic infiltrate following induction therapy as the only independent predictor for achievement of maintenance EI or HEMI helps clarify the clinical relevance of measuring histologic disease activity in UC. Epithelial neutrophilic infiltrate poses a means to stratify patients according to their likelihood of response to biologic treatment.
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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 | 0.002 | 0.003 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".