S856 Efficacy of Upadacitinib Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis by Biologic Inadequate Responder Status: Results From Two Randomized Phase 3 Studies
Bibliographic record
Abstract
Introduction: Upadacitinib (UPA), an oral JAK inhibitor, showed significantly greater efficacy vs placebo (PBO) in induction treatment of patients (pts) with moderately-to-severely active ulcerative colitis (UC) in two phase 3 induction trials, U-ACHIEVE and U-ACCOMPLISH. We evaluated efficacy of UPA in pts who had an inadequate response (IR), loss of response, or intolerance to biologic therapies (Bio-IR) or were non-Bio-IR. Methods: U-ACHIEVE and U-ACCOMPLISH, multicentre, double-blind, placebo (PBO)-controlled trials, randomized pts with moderately to severely active UC to UPA 45 mg QD or PBO for 8 weeks (wks). Randomization was stratified by status of previous biologic failure, ie an inadequate response (IR), loss of response, or intolerance to biologic therapies (Bio-IR or bio-failure) vs non-Bio-IR (non-bio-IR or non-bio-failure), baseline corticosteroid use (yes or no), and baseline adapted Mayo score (≤7 or >7). Efficacy endpoints included primary endpoint of clinical remission (adapted Mayo score) at Wk 8 and ranked secondary endpoints of clinical response (partial adapted Mayo score at Wk 2 and adapted Mayo score at Wk 8), endoscopic improvement (Mayo endoscopic subscore 0 or 1), endoscopic remission (Mayo endoscopic subscore 0) and histologic-endoscopic mucosal improvement at Wk 8 (HEMI; endoscopic subscore ≤1 and Geboes score ≤3.1). Results using non-responder imputation incorporating multiple imputation for missing data due to COVID-19 are reported. Results: In both studies, approximately half the pts were Bio-IR (Table 1). In both Bio-IR and non-Bio-IR pts, significantly higher proportion of pts receiving UPA achieved primary endpoint of clinical remission versus PBO; the magnitude of clinical remission at Wk 8 was greater in non-Bio-IR pts (UPA, 35% vs PBO, 9%; treatment difference [95% CI]: 26.0% [16.0, 36.1]) versus Bio-IR (UPA, 18% vs PBO, 0%; 17.5% [11.4, 23.6]) in U-ACHIEVE and non-Bio-IR (UPA, 38% vs PBO, 6%; 31.6% [22.8, 40.5]) versus Bio-IR (UPA, 30% vs PBO, 2%; 27.1% [19.6, 34.7]; Table 1) in U-ACCOMPLISH. Results were generally similar for ranked secondary endpoints (Table 1). UPA 45 mg QD was well-tolerated and no new safety signals were observed. Conclusion: UPA 45 mg QD is an effective induction treatment for pts with moderately to severely active UC. A significantly higher proportion of pts in both Bio-IR and non-Bio-IR groups receiving UPA achieved primary and secondary endpoints versus PBO. The magnitude of difference was greater among pts who were non-Bio-IR versus Bio-IR.Table 1.: Efficacy endpoints in Bio-IR and non-Bio-IR patients based on randomized treatment IR: inadequate response; Bio-IR: inadequate response, loss of response, or intolerance to biologic therapies. Clinical response at week 2 per partial adapted Mayo score (stool frequency subscore + rectal bleeding subscore). Clinical response at week 8 per adapted Mayo score (stool frequency subscore + rectal bleeding subscore + endoscopic subscore).
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".