S37 Efficacy and Safety of Upadacitinib Maintenance Therapy in Patients With Moderately to Severely Active Crohn’s Disease: U-ENDURE Phase 3 Results
Bibliographic record
Abstract
Background: Efficacy and safety of upadacitinib (UPA) 15 mg (UPA15) once daily (QD) and UPA 30 mg QD (UPA30) maintenance therapy in patients with Crohn’s disease (CD) were evaluated in U-ENDURE. Methods: Patients with moderate to severe CD who responded (≥30% decrease average daily very soft/liquid stool frequency [SF] and/or average daily abdominal pain score [APS], neither greater than baseline) to 12-weeks (wks) of UPA 45 mg QD induction therapy were eligible for U-ENDURE. At wk0, patients were randomized (1:1:1) to receive UPA15, UPA30 or placebo (PBO) as maintenance therapy for 52 wks1. Co-primary endpoints, clinical remission per CD activity index (CDAI) or SF/APS and endoscopic response, were evaluated at wk52. Other efficacy and safety outcomes were evaluated at or through wk52. Results: At wk52, greater proportion of patients receiving UPA15 (n = 169) and UPA30 (n = 168) vs PBO (n = 165) achieved clinical remission per CDAI (37.3% [95%CI: 30.0%, 44.6%] and 47.6% [40.1%, 55.2%] vs 15.1% [9.6%, 20.6%]) and SF/APS (35.5% [28.3%, 42.7%] and 46.4% [38.9%,54.0%] vs 14.4% [9.0%,19.8%]) (all P < 0.0001 vs PBO for both doses). UPA15 and UPA30 patients attained greater rates of endoscopic response vs PBO (27.6% [95%CI: 20.8%, 34.4%] and 40.1% [32.7%, 47.6%] vs 7.3% [3.3%, 11.2%]; P < 0.0001 vs PBO for both doses). UPA15 and UPA30 were superior vs PBO for key secondary endpoints at wk52 including clinical response (41.4% and 51.2% vs 15.2%), endoscopic remission (19.1% and 28.6% vs 5.5%), maintenance of clinical remission (per CDAI: 49.5% and 65.2% vs 21.2%; per SF/APS: 50.5% and 60.0% vs 19.6%), corticosteroid-free clinical remission in all patients (per CDAI, 36.7% and 46.4% vs 14.5%; per SF/APS, 34.9% and 44.6% vs 14.4%) and in patients with baseline steroid use (per CDAI, 39.7% and 39.7% vs 4.9%; per SF/APS, 38.1% and 38.1% vs 4.9%), clinical+endoscopic remission (per CDAI, 14.8% and 23.2% vs 3.7%; per SF/APS, 13.7% and 22.6% vs 4.3%), and change from baseline in IBDQ total score (LS mean[SE]: 59.3[3.22] and 64.5[3.15] vs 46.4[4.02]) (all P < 0.01 vs PBO for both doses). UPA30-treated patients also demonstrated significant improvement from baseline in FACIT-F vs PBO (LS mean[SE]: 16.1[1.02] vs 12.0[1.34]; P < 0.001). Rates of adverse events (AE) and serious AEs were similar across UPA groups; AE leading to treatment discontinuation rates were similar across groups. Most common AE was CD worsening (UPA15: 29.7 events/100 patient-years [E/100PY], UPA30: 12.0E/100PY, PBO: 58.0E/100PY). Serious infection rates were similar across groups (6.1-8.4 E/100PY); herpes zoster rate was higher in UPA30 (7.2E/100PY) vs PBO (4.7E/100PY) and UPA15 (4.0E/100PY). Malignancies excluding non-melanoma skin cancer (NMSC) were reported in 1 UPA15 patient and 2 UPA30 patients; all events were diagnosed within 9 months of first UPA exposure. One gastrointestinal perforation was reported in each group. One event of hepatic vein thrombosis was reported in UPA30. No deaths, tuberculosis, NMSC, or adjudicated cardiovascular events occurred in any group. Conclusion(s): Among patients with moderate to severe active CD who respond to UPA induction therapy, UPA15 and UPA30 maintenance treatments were well tolerated and superior to PBO for all clinical and endoscopic outcomes, and most quality-of-life outcomes at wk52.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".