P063 Interleukin-8 mucosal transcript as predictor of response to Vedolizumab treatment in Ulcerative Colitis: preliminary results from a prospective study
Bibliographic record
Abstract
Abstract Background Vedolizumab (VDZ) is a safe, well tolerated and efficient biologic agent used for the treatment of inflammatory bowel disease (IBD), as confirmed by phase 3 randomised controlled trials. However, primary non-response and secondary loss-of-response to VDZ represent a clinically significant problem. The objectives of the present study are to assess the differences in mucosal gene expression profiles of patients with Ulcerative Colitis (UC) prior to VDZ initiation and to identify transcriptomic biomarkers capable of discriminating responders and non-responders to VDZ treatment. Methods Mucosal samples were collected during colonoscopy from patients with UC prior to VDZ initiation. The minimum extension of disease for study inclusion was left-sided colitis (E2 Montreal), and patients had at least moderate flare of clinical activity based on the total Mayo Score. Patients were dichotomized based on clinical response at week 10 in responders and non-responders. Clinical response at week 10 was defined as a decrease with >50 percent for both rectal bleeding score and stool frequency score according to the latest STRIDE-II recommendations for short-term targets. A commercially available panel of primers for 84 genes associated with IBD were assessed on mucosal samples through quantitative PCR. Results Eight patients with previous failure to anti-TNF agents, were sampled prior to VDZ initiation. We identified 3 responders and 5 primary non-responders at week 10 after VDZ treatment initiation. We found 15 genes up-regulated in non-responders compared to responders with a trend towards statistical significance (p=0.057). The highest fold-change was obtained for CXCL8. Conclusion We identified 15 mucosal transcripts differentially expressed in VDZ primary non-responder UC patients. Of those, the highest fold change was observed for CXCL8. Enlarging the cohort might contribute to achievement of statistical significance for the data presented. CXCL8 up-regulation seems to predict lack of response to VDZ treatment and represents an interesting future therapeutic target in UC.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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 | 0.001 | 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".