S714 52-Week Risankizumab Subcutaneous Maintenance Dosing Is Efficacious and Well Tolerated in Patients With Moderate to Severe Crohn’s Disease Who Had Delayed Response to 12-Weeks IV Risankizumab Induction
Bibliographic record
Abstract
Introduction: In patients with moderate to severe Crohn's disease (CD), the ADVANCE and MOTIVATE phase 3 induction studies showed intravenous (IV) risankizumab (RZB), an anti-p19 interleukin-23 inhibitor, to be superior to placebo (PBO) for achieving clinical and endoscopic endpoints at Week (Wk) 12.1 Here, we evaluated the long-term efficacy and safety of RZB during the FORTIFY maintenance study in patients with delayed clinical response to IV RZB induction. Methods: Patients who did not achieve clinical response (defined as ≥30% decrease in average daily stool frequency [SF] and/or ≥30% decrease in average daily abdominal pain score [APS], both not worse than baseline of induction) following 12-wks IV RZB (600 mg or 1200 mg) induction dosing, but who did achieve clinical response at Wk 24 following an additional 12-wks RZB subcutaneous (SC) dosing (“delayed responders”) were examined. These patients continued on the same dose (RZB 180 mg SC [N = 30], RZB 360 mg SC [N = 33]) in the FORTIFY maintenance study and were analyzed for clinical and endoscopic improvements at Wk 52. Results: At FORTIFY Wk 52, most delayed responders achieved clinical remission and response with 180 mg or 360 mg RZB SC (Table, see footnotes for endpoint definitions). In addition, patients receiving RZB SC (180 mg or 360 mg) also achieved endoscopic response (36.7%, 45.5%), endoscopic remission (40.0%, 42.4%), deep remission (40.0%, 39.4%), ulcer free endoscopy (27.6%, 24.2%), and the combined endpoint of SF/APS clinical remission + endoscopic response (23.3%, 36.4%). Moreover, a dose-response trend was observed, with numerically higher response rates observed with RZB 360 mg SC relative to 180 mg SC for most outcomes, including clinical remission (CDAI and SF/APS), CDAI clinical response, enhanced clinical response, endoscopic response, endoscopic remission, and the composite endpoint of SF/APS clinical remission + endoscopic response. SC RZB maintenance dosing in delayed responders was well tolerated. The profile of treatment emergent adverse events was consistent with the known safety profile of patients with CD treated with RZB. No new safety risks were identified. Conclusion: RZB was efficacious in patients with delayed clinical response to RZB induction. These findings underscore the additional clinical benefit of SC RZB treatment in maintenance, even in patients who were initial non-responders to 12-wks IV RZB induction. RZB was well tolerated in delayed responders with no new safety risks identified. Table 1. - Efficacy and Safety after 52-Weeks Maintenance SC RZB Dosing in Delayed Responders (NRI-NCa) Responder GroupTreatment Group, n (%) [95% CI] CDAI Clinical Response Enhanced Clinical Response CDAI Clinical Remission SF/APS Clinical Remission Endoscopic Response Ulcer Free Endoscopy Endoscopic Remission SF/APS Clinical Remission and Endoscopic Response Deep Remission RZB 180 mg SC delayed responders, Wk 24 53.3(6/30)[35.5, 71.2] 56.7(17/30)[38.9, 74.4] 53.3(16/30)[35.5, 71.2] 43.3(13/30)[25.6, 61.1] 36.7(11/30)[19.4, 53.9] 27.6(8/29)[11.3, 43.9] 40.0(12/30)[22.5, 57.5] 23.3(7/30)[8.2, 38.5] 40.0(12/30)[22.5, 57.5] RZB 360 mg SC delayed responders, Wk 24 75.8(25/33)[61.1, 90.4] 66.7(22/33)[50.6, 82.8] 66.7(22/33)[50.6, 82.8] 54.5(18/33)[37.6, 71.5] 45.5(15/33)[28.5, 62.4] 24.2(8/33)[9.6, 38.9] 42.4(14/33)[25.6, 59.3] 36.4(12/33)[20.0, 52.8] 39.4(13/33)[22.7, 56.1] Responder GroupTreatment Group, (E/100PYs) Deaths Serious infections All treatment emergent adverse events AE related to COVID-19 Serious AE Hepatic events Injection site reactions AE leading to discontinuation of study drug Crohn's Disease RZB 180 mg SC (N=31) (PYs=27.5) delayed responders, Wk 24 0 0 132 (479.8) 0 6 (21.8) 0 6 (21.8) 2 (7.3) 7 (25.4) RZB 360 mg SC (N=33) (PYs=32.1) delayed responders, Wk 24 0 1 (3.1) 83 (258.9) 0 4 (12.5) 1 (3.1) 2 (6.2) 0 7 (21.8)
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".