OP01 PROFILE: a multi-centre, randomised, open-label, biomarker-stratified clinical trial of treatment strategies for patients with newly-diagnosed Crohn’s disease
Bibliographic record
Abstract
Abstract Background Clinical outcomes differ substantially between patients with Crohn’s disease and there is variability in how newly-diagnosed patients are managed. Recent interest has focused on developing biomarkers to predict outcomes and guide therapy. PROFILE was designed to evaluate the clinical utility of a blood-based prognostic biomarker in patients randomised to "top-down" or "accelerated step-up" treatment strategies for newly-diagnosed Crohn’s disease. Methods PROFILE (PRedicting Outcomes For Crohn's dIsease using a moLecular biomarker, ISRCTN 11808228) was an open-label, biomarker-stratified, randomised controlled trial. It enrolled adults with newly-diagnosed active Crohn’s disease (Harvey Bradshaw Index ≥7 and C-reactive protein > upper limit of normal or faecal calprotectin ≥200 ug/g, plus endoscopic evidence of active inflammation) in 40 UK hospitals. Following biomarker testing patients were randomised to "top-down" (infliximab/immunomodulator) or "accelerated step-up" (conventional) treatment stratified by: biomarker subgroup (termed IBDhi/IBDlo), endoscopic inflammation (mild/mod/severe) and extent (colonic/other). The primary endpoint was sustained steroid and surgery-free remission to week 48. The key secondary endpoint was endoscopic remission (absence of ulcers). The full analysis population (equivalent to ‘intention-to-treat’) was analysed. Results 386 patients were randomised from 29 December 2017 to 5 January 2022. Median time from diagnosis to trial enrollment was 12 days (0-191). Primary outcome data were available for 379 eligible participants. Sustained steroid and surgery-free remission was significantly more frequent in "top-down" (79% of 189 patients) compared to the "accelerated step-up" arm (15% of 190 patients), with an absolute difference of 64% (95% CI=57-72%, p<0.001). There was no biomarker-treatment interaction effect (absolute difference 1%, 95% CI=-14 - +14%, p=0.944). Endoscopic remission at week 48 was greater in "top-down" vs "accelerated step-up" (67% vs 44%, 95% CI=11-36%, p<0.001), with no biomarker-treatment interaction. Incidence of adverse events (including disease flares) and serious adverse events was lower in "top-down" vs "accelerated step-up" (168 vs 315; 16 vs 25 respectively), with fewer complications requiring abdominal surgery (1 vs 10, odds ratio=0.095, 95% CI=0.001-0.505) and no increase in infections. Conclusion "Top-down" treatment with combination infliximab/immunomodulator achieved substantially higher sustained steroid and surgery-free remission compared to "accelerated step-up". The biomarker did not show clinical utility in PROFILE. "Top-down" should now be considered standard-of-care for patients with newly-diagnosed active Crohn’s disease.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 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".