AODWE-006 Efficacy of ustekinumab for induction and maintenance of histological healing in patient’s with crohn’s disease
Bibliographic record
Abstract
Introduction Ustekinumab (UST) has been shown to induce and maintain clinical response and remission and to produce clinically meaningful endoscopic improvement in patients with moderate-severe Crohn’s disease (CD). Effects of UST on histologic CD activity were evaluated in a substudy of the induction (UNITI-1 and 2) and maintenance (IM-UNITI) Phase 3 studies. Method Biopsies were taken at induction baseline(I-Wk0), Wk8(I-Wk8), and maintenance Wk44(M-Wk44) from 3 sites (ileum, splenic flexure, rectum) and blindly scored by an expert GI pathologist (GDH) using the Global Histology Activity Score (GHAS1). At I-Wk0, pts received a single IV dose (UST 130 mg, UST~6 mg/kg, or PBO). At I-Wk8, UST induction responders were re-randomised to subcutaneous (SC) PBO, UST 90 mg q12w or UST 90 mg q8w. Histology data from 251 substudy pts with simple endoscopic score for CD (SES-CD)≥3 at I-Wk0 were eligible for analysis. The relationship between GHAS and SES-CD was evaluated by Spearman correlation. Histologic improvements were assessed within groups (UST, PBO) and between groups (UST vs. PBO, at I-Wk0, I-Wk8 and M-Wk44). Results Regional and overall GHAS were moderately correlated with SES-CD at all timepoints (r~0.6, p<0.001). GHAS was significantly reduced at I-Wk8 in pts treated with UST (from 10.4 to 7.1, p<0.001) but not PBO (from 9.2 to 7.8). At M-Wk44 in the randomised population, a continued reduction in GHAS from I-Wk8 was observed with UST 90 mg SC q8w (from 7.39 to 6.07, p=0.07) but not UST 90 mg SC q12w (from 5.29 to 8.67) or PBO (from 9.19 to 10.85). In the pooled maintenance population (randomised and non-randomised), continued histologic improvement from I-Wk8 was observed with UST 90 mg q8w (7.14 to 5.19, p<0.0001), but not UST 90 mg q12w (from 6.14 to 7.18) or PBO (from 8.19 to 8.85). Consistent results are observed in between-group (UST vs. PBO) analyses, numerically greater GHAS reduction was observed for UST. Conclusion Histologic and endoscopic disease activities were moderately correlated. Consistent with previously reported results, statistically significant histologic improvements were observed in pts induced with UST, but not PBO. Trends for greater and continued histologic improvement were observed in pts who received UST 90 mg q8w maintenance. Disclosure of Interest K Li Conflict with: Janssen R and D, D Chan Conflict with: Janssen R and D, P Pollack Conflict with: Janssen R and D, D Jacobstein Conflict with: Janssen R and D, C Brodmerkel Conflict with: Janssen R and D, C Gasink Conflict with: Janssen R and D, B Feagan: None Declared, W Sandborn: None Declared, P Rutgeerts: None Declared, G De Hertogh: None Declared
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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 | 0.001 |
| 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".