S739 Matching-Adjusted Indirect Comparison of Upadacitinib versus Vedolizumab as Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis
Bibliographic record
Abstract
Introduction: Aim is to conduct placebo(PBO)-anchored matching-adjusted indirect comparison (MAIC) of efficacy and safety outcomes between upadacitinib(UPA) and vedolizumab(VEDO) in patients(pts) with moderate to severe active UC. Methods: Data from phase 3 induction studies U-ACHIEVE Induction, U-ACCOMPLISH, and GEMINI 1 were used. Pts received UPA 45mg oral, once daily for 8 weeks; VEDO 300mg intravenous, at weeks 0 and 2; or corresponding PBO. Baseline characteristics for age, gender, duration of disease, total Mayo score, corticosteroid use, and fecal calprotectin levels from UPA trials were weighted to match that reported for pts in GEMINI for efficacy and previous anti-tumor necrosis factor/biologic therapy use/failure, Inflammatory Bowel Disease Questionnaire score, hemoglobin concentration, and white-cell count for safety. MAIC was done for bio-naïve(no exposure to any biologic at baseline) and bio-failure(inadequate response, loss of response, or intolerance to biologic treatment at baseline) pts for efficacy outcomes and all pts for safety outcomes. Efficacy outcomes evaluated at Week 6(VEDO)/Week 8(UPA) were clinical remission per full Mayo score(FMS; FMS≤2 with no subscore >1), clinical response per FMS(decrease from baseline in FMS≥3 points and ≥30%, accompanied by decrease in rectal bleeding score [RBS] of ≥1 or absolute RBS of 0 or 1), and endoscopic improvement(endoscopic subscore 0 or 1). Safety outcomes were all adverse events(AEs), serious AEs(SAEs), and serious infections. Results: MAIC used data from 833 UPA pts and 351 VEDO pts for efficacy; 848 and 374 pts for safety. A significantly greater proportion of pts receiving UPA vs VEDO in bio-naïve and bio-failure groups achieved clinical remission, clinical response, and endoscopic improvement after weighting(P < 0.05, Table). Rate differences between UPA and VEDO cohorts for clinical remission, clinical response, and endoscopic improvement were 0.160, 0.173, and 0.270, respectively, for bio-naïve group and 0.141, 0.374, and 0.191 for bio-failed cohort. Safety outcomes, including rates of AEs, SAEs, and serious infections, were not significantly different between UPA and VEDO. Conclusion: Greater clinical efficacy with comparable safety was achieved during induction treatment with UPA vs VEDO for pts with moderate to severe active UC based on MAIC, given caveat of differences in onset of action rates and assessment times of the drugs. Additional MAIC to assess longer-term outcomes are warranted. Table 1. - Efficacy/ safety outcome Treatment Rate a,b,c (Bio-naïve d ) Rate difference(95% CI)UPA or VEDO vs PBO(Bio-naïve d ) Rate difference(95% CI)UPA vs VEDO(Bio-naïve d ) Rate a, b,c (Bio-failed) Rate difference(95% CI)UPA or VEDO vs PBO(Bio-failed) Rate difference(95% CI)UPA vs VEDO(Bio-failed) Clinical remission UPA 45 mg /PBO 37.9%/5.4% 0.325(0.245, 0.405) 0.160** (0.038, 0.282) 20.7%/0.0% 0.207(0.156, 0.257) 0.141** (0.048, 0.233) VEDO 300 mg /PBO 23.1%/6.6% 0.165(0.074, 0.256) 9.8%/3.2% 0.066(−0.012, 0.143) Clinical response UPA 45 mg /PBO 81.4%/37.3% 0.441(0.332, 0.549) 0.173* (0.003, 0.343) 65.4%/9.6% 0.558(0.479, 0.637) 0.374*** (0.208, 0.540) VEDO 300 mg /PBO 53.1%/26.3% 0.268(0.137, 0.399) 39.0%/20.6% 0.184(0.038, 0.329) Endoscopic improve-ment UPA 45 mg /PBO 61.5%/10.3% 0.512(0.422, 0.601) 0.270*** (0.112, 0.427) 33.0%/4.0% 0.290(0.221, 0.358) 0.191* (0.034, 0.348) VEDO 300 mg /PBO 49.2%/25.0% 0.242(0.112, 0.372) 30.5%/20.6% 0.099(−0.043, 0.240) AE/SAE/Serious infections (overall population) UPA 45 mg /PBO AE: 55.0%/50.2%SAE: 2.9%/3.8%Serious infections: 0.6%/0.4% AE: 0.048 (−0.040, 0.136)SAE: −0.009 (−0.042, 0.023)Serious infections: 0.001 (−0.011, 0.014) AE: 0.111 (−0.024, 0.246)SAE: 0.036 (−0.019, 0.091)Serious infections: 0.017 (−0.010, 0.044) VEDO 300 mg /PBO AE: 40.0%/46.3%SAE: 2.2%/6.7%Serious infections: 0.4%/2.0% AE: −0.063 (−0.166, 0.039)SAE: −0.045 (−0.089, 0.000)Serious infections: −0.016 (−0.040, 0.008) aAfter weighting.bAggregated numbers from both induction studies.cUPA data are individual level results while VEDO data are aggregated.dEfficacy outcomes are based on bio-naïve pts and safety outcomes are based on the overall population. P-value equals *< 0.05, **≤0.01, ***< 0.001. Patient number (bio-naïve/bio-failed/all pts-safety): UPA 45 mg (262/292/562), placebo-UPA (132/147/286), VEDO (130/82/225), placebo-VEDO (76/63/149). AE, all adverse events; PBO, placebo; pts, patients; SAE, serious adverse events; UPA, upadacitinib; VEDO, vedolizumab.
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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 | 0.008 | 0.009 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.007 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".