S739 Matching-Adjusted Indirect Comparison of Upadacitinib versus Vedolizumab as Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis
Notice bibliographique
Résumé
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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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,008 | 0,009 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,007 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».