S1134 Association of Nonswitched Memory B-Cell (MBC) Levels With Ozanimod (OZA) Efficacy in Patients (Pts) With Moderately to Severely Active Crohn’s Disease (CD): Results From the Phase 2 STEPSTONE Study
Notice bibliographique
Résumé
Introduction: OZA is approved for the treatment (tx) of moderately to severely active ulcerative colitis and is under investigation for CD. Clinical, endoscopic, and histologic improvements were observed after 12wk of tx with OZA in pts with moderately to severely active CD in the phase 2 STEPSTONE study. Methods: This exploratory analysis of STEPSTONE assessed the association between levels of circulating lymphocyte subsets and OZA efficacy. Pts received OZA 0.92 mg for 12wk. Lymphocyte subsets were evaluated using multicolor flow analysis on blood samples collected before tx and at Week (W) 12; differences between Day 1 and W12 were analyzed by Wilcoxon signed-rank tests. Change in disease activity from baseline (BL) to W12 was determined for Simple Endoscopic Score for Crohn’s Disease, size of ulcers, extent of ulcerated surface, extent of affected surface, presence of narrowing, Crohn’s Disease Activity Index (CDAI), Robart’s Histopathology Index (RHI), Geboes Histology Activity Score (GHAS), and stool frequency. Efficacy outcomes were evaluated at W12. Associations of lymphocyte subset levels with disease activity changes and efficacy outcomes were assessed using Spearman’s correlation and logistic regression, respectively. Results: Of 69 pts enrolled, 52 had disease activity, efficacy outcome, and flow cytometry data at BL and W12 and were included in this analysis. Most lymphocyte subsets assessed were significantly associated with 1 or 2 efficacy outcomes. Nonswitched MBCs were significantly associated with most outcomes, including endoscopic response-25, endoscopic response-50, endoscopic remission, global GHAS remission, and RHI mucosal healing (Table 1). BL levels of nonswitched MBCs were significantly correlated with change from BL to W12 in extent of affected surface (Spearman’s rho [SR] = –0.44, P< 0.05), RHI (SR = –0.34, P< 0.05), and GHAS (SR = –0.47, P< 0.05). Changes in levels of nonswitched MBCs were significantly correlated with change from BL to W12 in CDAI (SR = 0.38, P< 0.05), RHI (SR = 0.37, P< 0.05), GHAS (SR = 0.43, P< 0.05), and stool frequency (SR = 0.43, P< 0.05). Conclusion: After 12wk of OZA tx, higher levels of nonswitched MBCs at BL were associated with endoscopic and histologic improvement, and reductions in nonswitched MBCs were associated with decreases in clinical and histologic disease activity. These data implicate nonswitched MBCs, which are involved in T cell–dependent immune responses and some inflammatory diseases, as a marker associated with OZA response in CD. Table 1. - Association of BL lymphocytes with W12 efficacy Lymphocyte subset Clinical responsea Clinical remissionb Endoscopic response-25c Endoscopic response-50d Endoscopic remissione Global GHAS remissionf RHI remissiong RHI mucosal healingh CD4 EM T cell; CD8 CM T cell NS; NS NS; NS NS; NS NS; NS NS; NS 0.0350 (–0.69); 0.0233 (–0.87) NS; NS NS; NS CD8 skin-homing CCR4 EM cell NS NS NS NS NS NS 0.0155 (0.15) NS CD8 TEMRA (fully differentiated) NS NS NS NS 0.0484 (0.61) 0.0138 (0.95) NS NS Naive CD8+ T cell NS NS NS 0.0449 (0.55) NS NS NS NS CD8 EM T cell NS NS NS NS NS 0.0344 (0.79) NS NS B cell NS NS NS 0.0404 (0.68) NS NS NS NS Nonswitched MBC NS NS 0.0368 (0.52) 0.0046 (0.86) 0.0163 (0.84) 0.0036 (1.20) NS 0.0136 (0.95) IgD-CD27 MBC NS NS NS NS NS 0.0159 (0.88) NS NS MBC NS NS NS NS NS 0.0403 (0.76) NS NS All lymphocyte subsets were measured in cells/µl. The values in each cell represent the P-value with logistic regression coefficient beta in parentheses.aCDAI reduction from BL of ≥100 points.bCDAI score of < 150.cDecrease of ≥25% in SES-CD from BL.dDecrease of ≥50% in SES-CD from BL.eSES-CD ≤4 points and SES-CD decrease ≥2 points with no SES-CD subscore >1 point.fNo active inflammation in any measured segment based on the GHAS.gNo active inflammation in any measured segment based on the RHI.hEndoscopic remission plus RHI remission.CM, central memory; EM, effector memory; NS, not specified; SES-CD, Simple Endoscopic Score for Crohn’s Disease; TEMRA, terminally differentiated effector memory.
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) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| 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 ».