S1451 Efficacy and Safety Profile of Etrasimod Was Not Impacted by Baseline Disease Activity: A Post Hoc Analysis of the ELEVATE UC Program
Notice bibliographique
Résumé
Introduction: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Methods: In this post hoc analysis of ELEVATE UC 52 (NCT03945188; treat-through design with 12-week [wk] induction then 40-wk maintenance periods) and ELEVATE UC 12 (NCT03996369; 12-wk induction period), etrasimod efficacy and safety were assessed according to baseline (BL) disease activity. Patients (pts) aged 16–80 years with moderately to severely active UC were randomized 2:1 to etrasimod 2 mg once daily or placebo (PBO).1 Pts’ BL UC activity was stratified as moderately or severely active based on a modified Mayo score (MMS) of 5–7 or 8–9, respectively. Efficacy endpoints including mean percentage change from BL in MMS and clinical response/remission per MMS category were measured at Wk12. Pooled efficacy data were analyzed descriptively; 95% confidence intervals (CIs) were calculated for all means or proportions with normal approximation or simultaneous estimation method, respectively. Safety was assessed up to Wk52 in the pooled safety analysis set. Results: Of the 743 pts in this analysis, 525 (70.7%) and 218 (29.3%) had a BL MMS of 5–7 and 8–9, respectively. BL characteristics were broadly similar across subgroups, except for lower rates of proctitis in pts with MMS 8–9 vs 5–7 (3.3% and 3.0% vs 9.3% and 9.4% in etrasimod and PBO groups, respectively; Table 1). At Wk12, pts taking etrasimod had larger mean percentage reductions (95% CI) in MMS vs PBO, regardless of BL disease activity (48.4% [52.3, 44.4] vs 27.0% [32.2, 21.7] for BL MMS 5–7, and 46.4% [51.2, 41.5] vs 29.8% [37.2, 22.3] for BL MMS 8–9). At Wk12, more pts taking etrasimod achieved clinical response vs PBO, regardless of BL disease activity, with an overall reduction from BL disease activity as measured by MMS categorization in both BL MMS subgroups (Figure 1). Proportions of pts with treatment-emergent adverse events (TEAEs) were broadly similar across treatment and BL disease activity subgroups (any TEAE: 59.0% vs 50.8% and 65.1% vs 56.1% for etrasimod vs PBO, in BL MMS 5–7 and 8–9 groups, respectively). Conclusion: Etrasimod showed greater reductions in disease severity and higher rates of clinical response, vs PBO, regardless of BL disease activity. Its safety profile was consistent with the overall trial population1 and was not impacted by BL disease activity. Reference: 1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171.Figure 1.: Proportion of pts achieving clinical response in each MMS category at Wk12 stratified according to baseline disease activity (pooled data from ELEVATE UC 52 and ELEVATE UC 12). [a]Clinical response was defined as a ≥ 2-point and ≥ 30% decrease from baseline in MMS, and a ≥ 1-point decrease from baseline in RBS, or RBS ≤ 1. [b]MMS was not available for some pts at Wk12 for various reasons, including discontinuation prior to Wk12. Data were pooled from ELEVATE UC 52 and ELEVATE UC 12. MMS, modified Mayo score; pt, patient; RBS, rectal bleeding subscore; UC, ulcerative colitis; Wk, Week. Table 1. - Demographics and baseline characteristics of patients in the ELEVATE UC clinical program[a] stratified according to baseline disease activity Baseline MMS 5–7 (moderate) Baseline MMS 8–9 (severe) Placebo QD(N = 181) Etrasimod2 mg QD(N = 344) Placebo QD(N = 66) Etrasimod2 mg QD(N = 152) Age (years), mean (SD)Female, n (%)Race, n (%)WhiteAsianBlack or African AmericanOtherDuration of UC (years), mean (SD)Proctitis,b n (%)Baseline MMS, mean ES of 3 at baseline, n (%)Baseline CS use, n (%)Naïve to biologic/JAKi, n (%) 40.3 (13.9)70 (38.7)154 (85.1)21 (11.6)2 (1.1)4 (2.2)7.0 (6.7)17 (9.4)6.3 86 (47.5)53 (29.3)126 (69.6) 40.6 (13.9)158 (45.9)278 (80.8)45 (13.1)7 (2.0)14 (4.1)7.5 (7.5)32 (9.3)6.3 144 (41.9)89 (25.9)240 (69.8) 37.6 (12.9)27 (40.9)53 (80.3)10 (15.2)3 (4.5)06.4 (6.1)2 (3.0)8.1 62 (93.9)19 (28.8)41 (62.1) 42.2 (13.8)69 (45.4)132 (86.8)16 (10.5)1 (0.7)3 (2.0)7.3 (7.1)5 (3.3)8.1 145 (95.4)58 (38.2)102 (67.1) aPooled for ELEVATE UC 52 and ELEVATE UC 12.bCentral read.CS, corticosteroid; ES, endoscopic subscore; JAKi, Janus kinase inhibitor; MMS, modified Mayo score; N, number of patients in the baseline disease activity subgroup by treatment; n, number of patients in the specified category; QD, once daily; SD, standard deviation; UC, ulcerative colitis.
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 | 0,003 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,003 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| 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 ».