O27 BMJ Open Gastroenterology best clinical science abstract: endoscopic outcomes from 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
Background Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn’s disease. We evaluated the clinical utility of a biomarker in patients randomised to either ‘top-down’ or ‘accelerated step-up’ therapy for newly-diagnosed, active Crohn’s disease. Here we focus on endoscopic outcomes. 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 elevated CRP or faecal calprotectin ≥200 ug/g, with active inflammation at endoscopy). Following biomarker testing patients were randomised to ‘top-down’ (infliximab/immunomodulator) or ‘accelerated step-up’ treatment stratified by: biomarker subgroup (termed IBDhi/IBDlo), endoscopic severity (mild/mod/severe) and extent (colonic/other). Ileo-colonoscopies were undertaken at baseline and week 48. Where possible they were video recorded, uploaded to Endoread® and centrally-read. The remainder were scored locally. The primary endpoint was sustained steroid and surgery-free remission to week 48 and the key secondary endpoint was endoscopic remission (absence of ulcers/SES-CD ulcer subscore=0) at week 48. Tertiary endoscopic endpoints included: endoscopic remission at week 48 using centrally-read videos only, endoscopic response at week 48 (≥50% improvement in SES-CD vs baseline), and deep endoscopic remission at week 48 (total SES-CD=0). The full analysis (‘intention-to-treat’) population was analysed. Results 386 patients were randomised from Dec 2017 to Jan 2022. Median time from diagnosis to trial enrollment was 12 days (0–191). Primary outcome data were available for 379 eligible participants, with sustained steroid and surgery-free remission being more frequent in ‘top-down’ compared to ‘accelerated step-up’ (79% vs 15%, absolute difference 64%, 95% CI=57–72%, p<0.001). No biomarker-treatment interaction was observed. By week 48, of the 190 patients on ‘accelerated step-up’ 85% were on immunomodulators and 41% had escalated to infliximab. Endoscopic remission at week 48 was assessed in 253 patients and was significantly greater in ‘top-down’ compared to ‘accelerated step-up’ (67% vs 44%, absolute difference 23%, 95% CI=11–36%, p<0.001). Respective proportions in endoscopic remission were 60% vs 45% where only the 166 centrally-read colonoscopies were considered. Endoscopic response at week 48 was more frequent in ‘top-down’ compared to ‘accelerated step-up’ (82% vs 63%), as was deep endoscopic remission (52% vs 37%). Conclusion ‘Top-down’ treatment with combination infliximab and immunomodulator achieved substantially better clinical and endoscopic outcomes at week 48 compared to ‘accelerated step-up’ therapy. The biomarker lacked clinical utility. ‘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 | 0.005 | 0.018 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.007 | 0.003 |
| Insufficient payload (model declined to judge) | 0.146 | 0.011 |
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".