S773 Rapidity of Symptom Control with Upadacitinib Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Results From Two Randomized Phase 3 Studies
Bibliographic record
Abstract
Introduction: Upadacitinib (UPA) is an oral, selective JAK inhibitor investigated for treatment of several immune-mediated inflammatory diseases, including ulcerative colitis (UC). Safety and efficacy of UPA in patients (pts) with moderately to severely active UC were studied in the phase 3 induction trials, U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026). We assessed early (week 2) symptomatic improvement and decrease in biomarkers of inflammation during induction therapy with UPA 45 mg once daily (QC) compared with placebo (PBO). Methods: In the multicentre, double-blind, PBO-controlled U-ACHIEVE and U-ACCOMPLISH trials, pts with moderately to severely active UC were randomized 2:1 to UPA 45 mg QD or PBO for 8 weeks. This analysis evaluated the proportions of pts with clinical remission (per partial Mayo score), clinical response (per partial Mayo score), stool frequency subscore (SFS) ≤1, and rectal bleeding subscore (RBS) of 0, as well as change from baseline in fecal calprotectin and high-sensitivity C-reactive protein (hsCRP) at week 2 with UPA vs PBO. Statistical comparison between the two groups was performed according to the Cochran-Mantel-Haenszel test adjusted for baseline corticosteroid use (yes or no), baseline Adapted Mayo score (≤7 or >7), according to prior biologic response (bio-IR, biologic inadequate response/bio failure; non-bio-IR, nonbiologic inadequate response/non-bio-failure). Results: As early as week 2, a significantly higher proportion of pts who received UPA achieved clinical remission per partial Mayo score (23%) compared with PBO (5%; treatment difference, [95% CI]: 17.4 [11.8, 23.1]; P < 0.001) in U-ACHIEVE. Results were similar in U-ACCOMPLISH at week 2: UPA (31%) versus PBO (3%); treatment difference (95% CI): 26.5 (20.9, 32.1; P < 0.001). Similarly, higher proportions of pts receiving UPA 45 mg QD achieved other efficacy endpoints, including clinical response, SFS ≤1 and RBS = 0, at week 2 vs PBO (Table 1). Significant decreases from baseline in markers of inflammation (fecal calprotectin and hsCRP levels) were also observed with UPA vs PBO in both trials (Table 1). Safety was comparable with the known safety profile of UPA, and no new safety signals were identified. Conclusion: UPA 45 mg QD achieved rapid improvement in both symptomatic and objective biomarker measures as early as week 2 compared with PBO in pts with moderately to severely active UC. The results demonstrate rapid onset of treatment effect with UPA.Table 1.: Baseline Clinical Characteristics of Patients with Perianal Crohn's Disease
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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 | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.004 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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".