Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease
Bibliographic record
Abstract
BACKGROUND: Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is under investigation for the treatment of Crohn's disease. METHODS: In two phase 3 induction trials (U-EXCEL and U-EXCEED), we randomly assigned patients with moderate-to-severe Crohn's disease to receive 45 mg of upadacitinib or placebo (2:1 ratio) once daily for 12 weeks. Patients who had a clinical response to upadacitinib induction therapy were randomly assigned in the U-ENDURE maintenance trial to receive 15 mg of upadacitinib, 30 mg of upadacitinib, or placebo (1:1:1 ratio) once daily for 52 weeks. The primary end points for induction (week 12) and maintenance (week 52) were clinical remission (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]) and endoscopic response (defined as a decrease in the Simple Endoscopic Score for Crohn's Disease [SES-CD; range, 0 to 56, with higher scores indicating more severe disease] of >50% from baseline of the induction trial [or for patients with an SES-CD of 4 at baseline, a decrease of ≥2 points from baseline]). RESULTS: A total of 526 patients underwent randomization in U-EXCEL, 495 in U-EXCEED, and 502 in U-ENDURE. A significantly higher percentage of patients who received 45-mg upadacitinib than those who received placebo had clinical remission (in U-EXCEL, 49.5% vs. 29.1%; in U-EXCEED, 38.9% vs. 21.1%) and an endoscopic response (in U-EXCEL, 45.5% vs. 13.1%; in U-EXCEED, 34.6% vs. 3.5%) (P<0.001 for all comparisons). At week 52 in U-ENDURE, a higher percentage of patients had clinical remission with 15-mg upadacitinib (37.3%) or 30-mg upadacitinib (47.6%) than with placebo (15.1%), and a higher percentage had an endoscopic response with 15-mg upadacitinib (27.6%) or 30-mg upadacitinib (40.1%) than with placebo (7.3%) (P<0.001 for all comparisons). Herpes zoster infections occurred more frequently in the 45-mg and 30-mg upadacitinib groups than in the respective placebo groups, and hepatic disorders and neutropenia were more frequent in the 30-mg upadacitinib group than in the other maintenance groups. Gastrointestinal perforations developed in 4 patients who received 45-mg upadacitinib and in 1 patient each who received 30-mg or 15-mg upadacitinib. CONCLUSIONS: Upadacitinib induction and maintenance treatment was superior to placebo in patients with moderate-to-severe Crohn's disease. (Funded by AbbVie; U-EXCEL, U-EXCEED, and U-ENDURE ClinicalTrials.gov numbers, NCT03345849, NCT03345836, and NCT03345823.).
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".