A205 EVALUATING THE ASSOCIATION BETWEEN PERIPHERAL BLOOD EOSINOPHILS AND DRUG RESPONSE IN CROHN'S DISEASE: CONTINUING ANALYSIS
Bibliographic record
Abstract
Abstract Background Th2 cytokines, IL-5 and IL-13 enhance peripheral and mucosal eosinophil survival, recruitment and degranulation, facilitating inflammation in Crohn's Disease. In a preliminary analysis, peripheral eosinophilia (PBE) is seen to have an association with rates of steroid response and anti-TNF response in CD patients. Participants with high PBE (> 200 cells/μL) appear to be more steroid-responsive but less responsive to Th1-targeting anti-TNF therapies. We hypothesize the pattern of PBE at CD diagnosis can help identify distinct subsets within a larger CD population and correlate with response to treatments such as prednisone or anti-TNFs. Purpose We aim to evaluate the pattern of PBE of CD patients at time of diagnosis (prior to drug exposure) and with each subsequent treatment; and if baseline PBE or any changes seen with drug exposures are predictive of treatment response. Method A retrospective cohort study is ongoing with CD patients exposed to glucocorticoids and an anti-TNF seen at 3 hospitals affiliated with University of Western Ontario. Patients were identified using administrative databases and reviewed for biochemical data (complete blood count) and disease activity (Harvey Bradshaw Index) at baseline, before and after each drug exposure. Participants were classified as having high PBE (eosinophils>200 cells/μL) versus low PBE (eosinophils <200 cells/μL). To date, 350 patients have been screened. Subgroup analyses of PBE > 300 cells/μL, and differences between female and male patients will be carried out. Result(s) 46 of 200 CD patients are included in the continuing analysis with a mean age of 45 years. 26 had PBE >200 cells/μL at baseline and 20 did not. The median number therapies used was 4 (IQR=0.75). All received glucocorticoids followed by an anti-TNF. There was no difference in the occurrence of hospitalization or surgery between the two groups. Overall 50% participants with high PBE >200 and >300 cells/μL had clinical response to glucocorticoid exposure, seen as a 3-point decrease in HBI compared to 45%, 47% in the low PBE cohort (n=13/26 vs. n=9/20 p=0.77; n=6/12 vs. n=16/34 p=1.0 respectively). With subsequent anti-TNF exposure, PBE rebounded in 7 participants. 36% patients in the high PBE group required anti-TNF dose escalation versus 24% in the low PBE group (n=9/25 vs. n=5/21, p=0.52). The proportion of patients with anti-TNF discontinuation was similar in both groups (high PBE 19.2%, n=5/26 vs. low PBE 15%, n=3/20, p=1.0). Men had higher steroid response rates compared to women in both high and low PBE groups (n=6/8 vs. n=8/18 p=0.21; n=4/9 vs. 4/11 p=1.0 respectively). Conclusion(s) Peripheral eosinophilia is seen in varying degrees in CD patients. Participants with high PBE are more steroid-responsive. High PBE patients overall were less responsive to anti-TNF therapies, requiring more dose-escalation and discontinued anti-TNF treatment. Completion of this study will help clarify the association between PBE in CD and treatment response. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest 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 | 0.003 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".