P593 Efficacy of Risankizumab in Patients With Moderately to Severely Active Ulcerative Colitis by Prior Advanced Therapy Failure and Mechanism of Action: Post Hoc Analysis of the INSPIRE and COMMAND Phase 3 Studies
Bibliographic record
Abstract
Abstract Background Risankizumab (RZB), a monoclonal antibody targeting interleukin-23 p19, demonstrated superior efficacy compared with placebo (PBO) in the induction and maintenance of patients with moderately to severely active ulcerative colitis (UC) in the INSPIRE and COMMAND studies. Here, we evaluated whether RZB was an effective induction and maintenance therapy based on the number (0, 1, ≥ 2) and types of prior advanced therapies (ATs). Methods Eligible patients with an Adapted Mayo Score of 5-9 points and endoscopic subscore of 2-3 (confirmed by central reading) were randomised 2:1 (intravenous [IV] RZB 1200 mg [RZB1200] or PBO) for 12 weeks (wks) in the phase 3 induction substudy of INSPIRE. Clinical responders (per Adapted Mayo Score) to RZB IV treatment in phase 2b and phase 3 induction were randomised 1:1:1 (subcutaneous [SC] RZB 180 mg (RZB180), SC RZB 360 mg (RZB360), or withdrawn to PBO [withdrawal, WD]) for 52 wks in COMMAND. Efficacy and safety outcomes were assessed at induction wk 12 and maintenance wk 52 in patients who were non-advanced therapy-inadequate responders (non-AT-IR), had 1 or ≥ 2 AT failures, and among patients previously treated with tumor necrosis factor inhibitors, vedolizumab, or Janus kinase inhibitors. Results Proportions of AT-IR patients were similar across treatment groups for the induction (RZB1200 51.2% [333/650]; PBO 52.3% [170/325]) and maintenance studies (RZB180: 74.9% [134/179]; RZB360: 74.7% [139/186]; PBO [WD] 75.4% [138/183]). Significantly greater proportions of patients receiving RZB achieved the primary endpoint of clinical remission per Adapted Mayo Score at wk 12 vs PBO in the non-AT-IR and AT-IR subgroups (RZB1200: 29.7%, 11.4% vs PBO: 8.4%, 4.3%, respectively); consistent results were observed at wk 52 in patients treated with either RZB maintenance dose vs PBO (RZB180: 50.9%, 36.6%; RZB360: 61.7%, 29.5%; vs PBO [WD] 31.1%, 23.2%, respectively) (P ≤ .05, Fig. 1-2). Regardless of the number of prior AT failures or class of prior therapy, numerically higher proportions of patients treated with RZB achieved clinical remission, clinical response, endoscopic improvement, and histologic endoscopic mucosal improvement at wk 12 of induction and wk 52 of maintenance. Rates of treatment-emergent adverse events were similar among subgroups in induction and maintenance. Conclusion RZB induction and maintenance therapy was effective and well-tolerated in patients with moderately to severely active UC regardless of a patient’s prior experience with advanced therapies. Numerically higher efficacy was observed in non-AT-IR compared to AT-IR subgroups.
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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 | 0.012 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.006 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".