| Title: |
OP01 PROFILE: a multi-centre, randomised, open-label, biomarker-stratified clinical trial of treatment strategies for patients with newly-diagnosed Crohn’s disease |
| Authors: |
Noor, N; Lee, J; Bond, S; Dowling, F; Brezina, B; Patel, K; Ahmad, T; Banim, P; Cooney, R; De La Revilla Negro, J; de Silva, S; Din, S; Durai, D; Gordon, J; Irving, P; Johnson, M; Kent, A; Kok, K B; Moran, G; Patel, P; Probert, C; Raine, T; Saich, R; Seward, A; Sharpstone, D; Smith, M; Subramanian, S; Upponi, S; Wiles, A; van den Brink, G; Vermeire, S; Jairath, V; D'Haens, G; McKinney, E; Lyons, P; Lindsay, J; Kennedy, N; Smith, K; Parkes, M |
| Source: |
Journal of Crohn's and Colitis ; volume 18, issue Supplement_1, page i1-i2 ; ISSN 1873-9946 1876-4479 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2024 |
| Description: |
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 |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/ecco-jcc/jjad212.0001 |
| Availability: |
https://doi.org/10.1093/ecco-jcc/jjad212.0001; https://academic.oup.com/ecco-jcc/article-pdf/18/Supplement_1/i1/57387547/jjad212.0001.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.B7357C34 |
| Database: |
BASE |