S1145 Corticosteroid-Free Efficacy Outcomes in Patients Receiving Concomitant Corticosteroids at Baseline in the Etrasimod ELEVATE UC 52 Trial
Notice bibliographique
Résumé
Introduction: Etrasimod is an investigational, oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). In ELEVATE UC 52 (NCT03945188), etrasimod was superior to placebo (PBO) in achieving Week (Wk) 52 corticosteroid (CS)-free clinical remission (CR).1 Methods: This post hoc analysis reports CS-free efficacy and safety in patients (pts) on baseline (BL) CS. Pts were randomized 2:1 to once-daily etrasimod 2 mg or PBO using a treat-through design (12-wk induction and 40-wk maintenance period). At entry, pts could receive concomitant CS (prednisone [≤ 20 mg/day], budesonide [≤ 9 mg/day] or equivalent) if on a stable dose ≥ 4 wks immediately before screening endoscopy; from Wk 12, CS tapering was recommended. CS-free was defined as withdrawal of CS ≥ 12 wks prior to assessment timepoint. CS-free outcomes assessed were CS-free CR at Wk 52, CS-free endoscopic improvement (EI) at Wk 52, and CR at Wk 12 + CS-free CR at Wk 52. From Wk 12, 4-wk CS-free symptomatic remission (SR; 4 wk in contrast to ≥ 12-wks CS free) was analyzed at each visit. Logistic regressions examined associations with CS-free efficacy at Wk 52. Safety was assessed. Results: At BL, 32.2% (93/289) and 29.2% (42/144) of etrasimod and PBO pts received CS; of these, significantly more etrasimod vs PBO pts achieved CS-free CR at Wk 52, CS-free EI at Wk 52 and CR at Wk 12 + CS-free CR at Wk 52 (all P < 0.05; Table 1). At Wks 40–52, there were significant differences (16.6–26.6%; P < 0.05) in 4-wk CS-free SR between etrasimod and PBO. In this subpopulation, being biologic/Janus kinase inhibitor-naïve was not a significant predictor of 12-wk CS-free CR at Wk 52 (odds ratio [OR]: 3.61; 95% confidence interval [CI] 0.91, 14.39; P=0.07); age, per 10-year increase, was significantly associated (OR: 1.51; 95% CI 1.03, 2.22; P=0.04). Etrasimod vs PBO pts with concomitant CS at BL experienced slightly more adverse events (AEs; not exposure adjusted) (71.0% [66/93] vs 61.9% [26/42]) but fewer serious AEs (6.5% [6/93] vs 14.3% [6/42]), including serious infections (0% [0/93] vs 7.1% [3/42]). Conclusion: More etrasimod vs PBO pts who received CS at BL met CS-free efficacy endpoints. Four-wk CS-free SR with etrasimod was superior to PBO from Wk 40. Concomitant CS use at BL had no notable negative effect on the safety of etrasimod, consistent with the overall ELEVATE UC 52 population. Reference: 1. Sandborn WJ et al. Lancet 2023; 401: 1159-1171.1 Table 1. - CS-Free Efficacy in Pts Receiving Concomitant CS at BL of ELEVATE UC 52 (FAS) Etrasimod 2 mg QD, n/N (%) PBO QD, n/N (%) Adjusted difference % (95% CI) p [a] 12-wk CS-free clinical remission at Wk 52 29/93 (31.2) 3/42 (7.1) 23.2 (10.6, 35.7)0.0003 12-wk CS-free endoscopic improvement at Wk 52 35/93 (37.6) 8/42 (19.0) 17.5 (2.5, 32.5)0.0226 CR at Wk 12 + CS-free CR at Wk 52 18/93 (19.4) 2/42 (4.8) 14.3 (3.5, 25.1)0.0092 All pts in the FAS had a modified Mayo score from 4 to 9 at BL. Clinical remission was defined as SFS=0 (or 1 with a ≥ 1-point decrease from BL), RBS=0 and ES ≤ 1 (excluding friability). Endoscopic improvement was defined as ES ≤ 1 (excluding friability).[a] Adjusted difference (%) is based on estimated common risk difference using Mantel-Haenszel weights; p is 2-sided to test the hypothesis of the adjusted risk difference being 0.BL, baseline; CR, clinical remission; CS, corticosteroid; ES, endoscopic subscore; FAS, full analysis set; n, number of unique pts achieving each endpoint; N, total number of pts in the analysis; PBO, placebo; pt, patient; QD, once daily; RBS, rectal bleeding subscore; SFS, stool frequency subscore; Wk, week.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,001 |
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 ».