DOP18 Efficacy of risankizumab versus ustekinumab by baseline Crohn’s Disease location: post-hoc analysis of the SEQUENCE head-to-head trial
Bibliographic record
Abstract
Abstract Background In Crohn’s disease (CD), disease location may impact treatment effect. This post-hoc analysis of the SEQUENCE head-to-head trial (NCT04524611) compared the efficacy of risankizumab (RZB), an interleukin (IL)-23 p19 inhibitor, versus ustekinumab (UST), an IL-12/23 p40 inhibitor, by CD location. Methods SEQUENCE was an open-label, efficacy assessment-blinded, randomized controlled trial, which enrolled patients (pts) with moderate to severe CD who previously failed ≥1 anti-tumor necrosis factor (TNF) therapy. Pts included in the primary efficacy analysis were randomised 1:1 to receive RZB (selected dosing: intravenous 600 mg induction dose administered at weeks (wks) 0, 4, and 8, followed by subcutaneous 360 mg maintenance dose every 8 wks starting at wk 12) or UST (a single weight-based induction dose administered at wk 0, followed by subcutaneous 90 mg maintenance dose every 8 wks starting at wk 8. A mandatory steroid taper began at wk 2. The primary endpoints were clinical remission (CD Activity Index <150) at wk 24 and endoscopic remission (Simple Endoscopic Score for CD ≤4 and at least a 2-point reduction versus baseline and no subscore >1 in any individual variable, as scored by a central reviewer blinded to treatment allocation) at wk 48. In this post-hoc analysis, both endpoints were evaluated in 100% of pts included in the primary efficacy analysis, stratified by baseline CD location subgroups (ileal only, colonic only, ileal-colonic). Nominal P-values were reported for treatment differences within subgroups. Results At baseline, majority of pts had either ileal-colonic (225 [43.3%]) or colonic (208 [40%]) CD; 87 (16.7%) pts had isolated ileal disease. At wk 24, numerically greater proportions of pts achieved clinical remission with RZB versus UST, regardless of disease location (treatment difference [95% confidence interval], P-value: ileal only, Δ0.8 [-20.1, 21.7], P=0.941; colonic only, Δ22.4 [9.2, 35.5], P=0.001; ileal-colonic, Δ18.2 [5.3, 31.0], P=0.007) (Figure). Pts randomized to RZB with colonic only disease had numerically higher rates of clinical remission relative to pts with ileal only or ileo-colonic disease. At wk 48, RZB-treated pts demonstrated numerically higher rates of endoscopic remission than UST-treated pts (ileal only, Δ22.5 [4.4, 40.6], P=0.017; colonic only, Δ18.3 [6.6, 30.0], P=0.003; ileal-colonic, Δ10.3 [-0.2, 20.9], P=0.057) (Figure). Endoscopic remission rates in the RZB-treated pts were generally similar between ileal only and colonic only CD. Conclusion In pts who have failed ≥1 anti-TNF therapy, RZB demonstrated greater rates of endoscopic remission compared to UST regardless of CD location, and greater rates of clinical remission in ileo-colonic and colonic CD.
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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 | 0.009 | 0.007 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.006 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.014 | 0.002 |
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".