Predictors of Outcome of Treatment of Pediatric Crohn's Disease with 6‐Mercaptopurine or Azathioprine
Bibliographic record
Abstract
Supported by a grant from NASPGHAN, with funds from the American Board of Pediatrics, and by GCRC grant M01 RR00109 Background: The thiopurine analogue antimetabolites 6-mercaptopurine (6MP) and its prodrug azathioprine (AZA) have demonstrated efficacy for maintenance of remission in patients with Crohn's disease. Aim: The aim of this study is to identify the predictors of a successful outcome of treatment with 6MP or AZA and to identify methods of utilizing these drugs that could be broadly applied to this patient population. Methods: Data are being obtained from a prospective analytic cohort of children and adolescents ages 1 to 17 years old with Crohn's disease who are initiating treatment with 6MP or AZA. Patients taking infliximab or other immunomodulators are excluded. We report a preliminary analysis of 60 patients who have been treated for 6 months. Independent variables (predictors) analyzed are gender, age, duration since diagnosis, indication for treatment, baseline disease activity (Harvey-Bradshaw Index, HBI; Physician Global Assessment, PGA), corticosteroid treatment, measurement of thiopurine methyltransferase (TPMT), measurement of 6MP metabolites and level of 6-thioguanine nucleotides (6TGN). Web-based data entry was performed by PIBDNet, a network of pediatric gastroenterologists at 75 sites in 38 states and provinces in the USA and Canada and 1 site in Australia. Results: The patients were 3 to 17 years old (median 12.5 years), 38% female, with 70% diagnosed <3 months prior to starting treatment with 6MP/AZA. The most common indication for treatment was induction or early therapy (61%). TPMT was measured in 65% prior to starting 6MP/AZA. At baseline the HBI was <5 in 68% of patients (median=3); the PGA was inactive disease in 5% of patients, mild in 48%, moderate in 38% and severe in 8%. After 6 months of treatment, the HBI was <5 in 88% (median=1) (p=0.002) and PGA had improved to 42% inactive, 43% mild, 12% moderate and 3% severe (p<0.001). With 6MP/AZA treatment, corticosteroid usage decreased from 68% to 25% of patients (p<0.001). Logistic regression and cumulative logit model found significant predictors of a favorable outcome were a higher HBI at baseline (p<0.001), steroid dependence (p=0.05) or avoidance of steroid therapy (p=0.02) as an indication for treatment, and 6TGN ≥230 pmoles/8 x 108 RBC (p=0.009). Conclusions: Preliminary data suggest that pediatric Crohn's disease patients with higher disease activity, steroid dependence or avoidance of steroid therapy as an indication for therapy, and 6TGN levels ≥230 are more likely to have a favorable response to treatment with 6MP or AZA.
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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 | 0.004 |
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".