S754 Risankizumab as Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease Who Failed 1 vs >1 Prior Biologic Treatment: Results From the MOTIVATE Study
Bibliographic record
Abstract
Introduction: Risankizumab (RZB), a monoclonal antibody against IL-23, a key cytokine in inflammatory bowel disease, has shown efficacy in patients (pts) with Crohn's disease (CD). Methods: MOTIVATE (NCT03104413), a double-blind randomized phase 3 study, enrolled pts with moderate to severe CD (CDAI 220-450, average daily [liquid/very soft] stool frequency [SF] ≥4 and/or daily abdominal pain score [APS] ≥2, and Simple Endoscopic Score for CD [SES-CD] ≥6 [≥4 for isolated ileal disease] excluding the narrowing component) who were randomized 1:1:1 to receive intravenous RZB 600/1200 mg, or placebo (PBO) at Wks 0, 4, and 8. Randomization was stratified by number of biologics failed, baseline (BL) steroid use, and SES-CD. Pts that failed ustekinumab was capped at 20%. Co-primary endpoints were clinical remission (per US protocol, CDAI < 150; per ex-US protocol, average daily SF ≤2.8 and daily APS ≤1, not worse than BL for both) and endoscopic response (decrease in SES-CD >50% from BL [or for pts with isolated ileal disease and BL SES-CD of 4, at least a 2-point reduction from BL]) at Wk 12. Safety was assessed in pts on at least 1 dose of study drug. Results: Total 569 pts were included in intent-to-treat (ITT) population (failed 1 biologic, n=268; failed >1 biologic, n=301). Significantly more pts in RZB 600/1200 mg groups vs PBO (P≤0.001) achieved co-primary endpoints (CDAI clinical remission: 42.5% and 40.3% vs 19.8%; SF/APS clinical remission: 34.6% and 39.3% vs 19.3%; endoscopic response: 28.8% and 34.2% vs 11.2%) (Table). RZB showed efficacy independent of number of biologics failed, with numerically more pts that failed only 1 biologic achieving primary endpoint than those that failed >1. Treatment emergent adverse event (AE) rates were numerically lower in the RZB 600/1200 mg groups (47.1% and 59.0%) vs PBO (66.2%), including serious AEs (4.9% and 4.4% vs 12.6%), AEs leading to study drug discontinuation (1.0% and 2.4% vs 8.2%), and serious infections (0.5% and 1.0% vs 2.4%), with some differences due to uncontrolled CD activity. No adjudicated major adverse cardiovascular events, tuberculosis, or adjudicated anaphylaxis were reported. One death was reported in a pt with squamous cell lung carcinoma in RZB 1200 mg group. Conclusion: RZB 600 mg and 1200 mg was more effective than placebo at inducing clinical remission and endoscopic response at week 12 in moderate to severe CD pts. Both RZB doses were generally well-tolerated, and AEs were consistent with the known safety profile of RZB.Table 1.: Part I: Univariable analysis of percentage time spent on monotherapy and correlation with clinical endpoints (significant values bolded and italicized) Part II: Distribution of Patients based on treatment strategy.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".