S897 Impact of Mirikizumab Therapy on Histologic Measures of Intestinal Inflammation in a Phase 2 Study of Patients With Moderately- to Severely-Active Crohn’s Disease
Bibliographic record
Abstract
Introduction: Mirikizumab(miri), a p19-directed IL-23 antibody, showed efficacy and was well-tolerated in phase2 randomized clinical trial(NCT02891226) in patients(pts) with Crohn’s disease(CD). We present histologic results at Week(W)12 induction and W52 maintenance. Methods: Pts were randomized 2:1:1:2 across 4 treatment arms(PBO, 200, 600, 1000mg miri) administered intravenously(IV) every 4W(Q4W) at W0, 4, 8. Pts receiving miri and achieving ≥1 point improvement from baseline(BL) at W12 in SES-CD were re-randomized 1:1 into double-blind maintenance to continue their IV dose assignment Q4W(IV/IV) or to 300mg miri SC Q4W(IV/SC); maintenance IV arms were pooled for analysis. W12 non-improvers and all induction PBO pts received 1000mg miri Q4W from W12 through W52. Biopsies from terminal ileum and 4 colonic segments(ascending, transverse, descending, rectum)were obtained during endoscopy at W0, 12, 52 and scored blind to treatment and response status. Ileum and colon scores were reported separately. Colon scores were derived from sum of 4 colonic segments; total intestine scores from 4 colonic segments plus ileum. Endpoints were defined post-hoc but prior to performing analyses and only included pts with active histologic disease at BL (Table 1). Histologic response: a) absence of neutrophils in lamina epithelialis, absence of epithelial damage, erosions and ulceration or b) decrease of either RHI or GHAS ≥50% from BL. Histologic remission: absence of mucosal neutrophils, epithelial damage, erosions, and ulceration. Deep histologic remission: histologic remission combined with absence of chronic inflammatory cell infiltration of lamina propria. To assess total intestine inflammation, the criteria for response, remission or deep remission must have been met in all 5 bowel segments. Results: At W12, histologic response and remission were significantly higher in all segments of 1000mg group vs PBO(response: ileum p< 0.01, total intestine p< 0.01, colon p< 0.05; remission: ileum p< 0.05, colon p< 0.05, total intestine p< 0.01). Among W12 improvers, both histologic response and histologic remission at W52 were similar in ileum and colon in IV/IV group, but lower in ileum than colon in IV/SC group. All but 2 pts with remission at W52 were in deep histologic remission. Conclusion: Pts treated with miri achieved and sustained histologic response and remission over 52 weeks of treatment. Among pts with W52 histologic remission, all but 2 pts achieved deep remission.Table 1.: Week 12 and week 52 histologic outcomes.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".