DOP71 Effects of ustekinumab induction therapy on endoscopic and histological healing in the UNIFI Phase 3 study in ulcerative colitis
Bibliographic record
Abstract
Ustekinumab (UST) is an effective therapy for moderate–severe UC; however, data regarding histological healing and the combination of histological and endoscopic healing (also described as endoscopic improvement in the appearance of the mucosa) are unknown. We evaluated the effects of UST on histological and endoscopic activity in the UNIFI Ph3 induction study of UST in moderate–severe UC(n = 961). Two colonic biopsies were collected from distal colon at screening and induction Wk8. Subjects not in response to placebo (PBO) at Wk8 received UST 6 mg/kg IV, and those not in response to UST IV received UST 90 mg SC; biopsies were obtained at Wk16. Endoscopic healing (EH; also described a endoscopic improvement in the appearance of mucosa) was defined as a Mayo endoscopy score <1; histological healing (HH) comprised the following Geboes score-based criteria: absence of erosion or ulceration, absence of crypt destruction, and <5% of crypts with epithelial neutrophil infiltration. To encompass both macro- and microscopic scales, histo-endoscopic mucosal healing (HEMH) was defined as achieving both EH and HH. At Wk8, EH was achieved in 26.6% and 13.8% of subjects treated with UST (combined 130 mg and 6 mg/kg IV doses)and PBO, respectively (adjusted tx difference, 12.8%; 95% CI, 7.9–17.8; p < 0.001). HH was achieved in 36.8% and 21.9% of UST and PBO-treated subjects, respectively (adjusted tx difference, 15.0%; 95% CI, 9.0–21.0; p < 0.001). Histo-endoscopic mucosal (HEMH) was achieved in 19.3% and 8.9% of UST and PBO-treated subjects, respectively (adjusted tx difference, 12.5%; 95% CI, 6.2–14.8; p < 0.001). Similar rates of EH, HH, and HEMH were achieved following induction with UST 130 mg or 6 mg/kg IV. Subjects not in response to PBO or UST at Wk8 were treated with UST at that time and re-evaluated at Wk16; of these, 12.1% and 16.5% of subjects who initially received UST or PBO IV, respectively, achieved HEMH. HH at Wk8 or Wk16 (irrespective of induction tx) was significantly associated with EH and HEMH (p < 0.001) and with both absolute levels and post-tx changes in Mayo score, partial Mayo score, and Mayo symptom sub-scores for stool frequency and rectal bleeding. Table 1. Clinical outcomes for subjects with or without histological healing at Week 8 and Week 16 in the UNIFI Phase 3 induction study Among subjects with moderately–severely active UC, those receiving IV UST induction had higher rates of EH, HH, and HEMH than those receiving PBO. Approximately 10% of subjects who did not achieve clinical response 8 weeks after IV UST achieved HEMH following a second (SC) dose. HH is associated with reductions in clinical and endoscopic disease activity as well as patient-reported symptoms.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".