S933 Durability of Symptomatic and Clinical Outcomes in Ozanimod-Treated Patients by Endpoints of Increasing Objectivity at True North Week 52: Interim Analysis of the True North Open-Label Extension Study
Notice bibliographique
Résumé
Introduction: Ozanimod (OZA) is approved for the treatment (tx) of moderately to severely active ulcerative colitis per results of the phase 3 True North (TN) study. Data from the ongoing open-label extension (OLE) demonstrated durability of efficacy in symptomatic, clinical, and mucosal endpoints up to 3 y with continuous OZA tx in patients (pts) who were clinical responders at TN Week (W) 52. Methods: This interim analysis of the TN OLE (cutoff: 10Jan2022) explored whether achieving endpoints at TN W52, examined by increasing objectivity, would impact the durability of symptomatic and clinical outcomes with continuous OZA tx up to OLE W94. OZA clinical responders at TN W52 who continued in the OLE were included in this analysis (N=131). These pts were categorized into subgroups based on achieved endpoints of increasing objectivity (ie, clinical response [CRes], clinical remission [CRem], endoscopic improvement, complete endoscopic healing [endoscopy score=0], histologic remission, mucosal healing, and stringent mucosal healing) at TN W52 to determine whether these endpoints at TN W52/OLE baseline influence the proportion of pts maintaining symptomatic (ie, total/partial Mayo scores and symptomatic CRes) and clinical (ie, CRes, CRem, or corticosteroid [CS]–free remission) outcomes in the OLE. OLE outcomes were assessed up to OLE W94 using observed case (OC) and nonresponder imputation (NRI) analyses. Results: Of 131 pts in this analysis, 114 (87%) completed OLE W46 and 94 (72%) completed OLE W94. OC analyses showed that partial and total Mayo scores and symptomatic CRes were similar and sustained over 94 wk of continuous OZA tx during the OLE, regardless of endpoint achieved at TN W52. Likewise, maintenance of CRes at OLE W46 and OLE W94 was not impacted by the achievement of endpoints of increasing objectivity at TN W52 (Table 1). Achievement of CRem at TN W52 had an incremental benefit over CRes at TN W52 for the maintenance of CRem and CS-free remission at OLE W94, but other endpoints of higher objectivity had no additional benefit (Table 1). A similar pattern was observed for NRI analyses. Clinical outcomes were sustained from OLE W46 to OLE W94 regardless of endpoint achieved at TN W52: CRes: 71.4%–78.4%; CRem: 65.2%–70.0%; and CS-free remission: 63.6%–70.6%. Conclusion: Symptomatic response and clinical outcomes with OZA were durable up to OLE W94. Maintenance of these long-term outcomes was not notably impacted by the achievement of increasingly more objective measures of responsiveness at TN W52. Table 1. - Endpoints (increasing in objectivity) at TN W52 (OC analysis) Endpoint, % (n/N) CResa CRemb CS-free remissionc OLE W46 OLE W94 OLE W46 OLE W94 OLE W46 OLE W94 CResa (N=131) 95.9 (93/97) 91.4 (74/81) 72.2 (70/97) 69.1 (56/81) 70.1 (68/97) 67.9 (55/81) CRemb (N=83) 97.0 (64/66) 94.4 (51/54) 81.8 (54/66) 75.9 (41/54) 80.3 (53/66) 74.1 (40/54) Endoscopic improvement (MES ≤1; N=93) 97.3 (73/75) 95.2 (60/63) 78.7 (59/75) 73.0 (46/63) 77.3 (58/75) 71.4 (45/63) Complete endoscopic healing (MES=0; N=50) 97.6 (40/41) 90.9 (30/33) 82.9 (34/41) 69.7 (23/33) 80.5 (33/41) 66.7 (22/33) Histologic remission (Geboes index score < 2.0; N=68) 98.1 (51/52) 95.3 (41/43) 82.7 (43/52) 74.4 (32/43) 80.8 (42/52) 72.1 (31/43) Mucosal healing (MES ≤1 and Geboes index score < 2.0; N=61) 97.9 (46/47) 94.7 (36/38) 80.9 (38/47) 71.1 (27/38) 78.7 (37/47) 68.4 (26/38) Stringent mucosal healing (MES=0 and Geboes index score < 2.0; N=37) 96.6 (28/29) 91.3 (21/23) 79.3 (23/29) 65.2 (15/23) 75.9 (22/29) 60.9 (14/23) Denominators for the OC analysis were based on the numbers of pts who completed OLE W46 or OLE W94 and had data available for the endpoints in question. aClinical response: reduction from baseline in the 9-point Mayo score of ≥2 points and ≥35%, and a reduction from baseline in RBS of ≥1 point or an absolute RBS of ≤1 point. bClinical remission: RBS=0, SFS ≤1 point (and a decrease of ≥1 point from the baseline SFS), and endoscopy subscore ≤1 point. cCS-free remission: Clinical remission while off CS for ≥12 wk. MES, mucosal endoscopy subscore; RBS, rectal bleeding subscore; SFS, stool frequency subscore.
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 | 0,006 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,002 |
| 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 | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».