S901 Group-Based Trajectory Modeling to Identify Response Patterns to Ozanimod Treatment in Patients With Ulcerative Colitis
Notice bibliographique
Résumé
Introduction: Ozanimod (OZA) is approved for the treatment (tx) of moderately to severely active ulcerative colitis (UC) in adults. In the phase 3 True North (TN; NCT02435992) study, patient (pt) responses to OZA were heterogenous at Week (W) 52. Methods: This TN post hoc analysis used grouP-based trajectory modeling (GBTM) to identify patterns of OZA response trajectories during the TN maintenance period (MP) in W10 OZA clinical responders who were rerandomized to continue OZA (OZA/OZA arm; n=230) in MP. Change from baseline (BL; TN W0) in partial Mayo score (PMS) was used as a variable for identifying pt clusters with various OZA response patterns. GBTM, determined by maximum likelihood estimation, was used to estimate OZA response trajectories. After modeling, clinical and mucosal outcomes at W52 were compared in the GBTM-identified pt clusters. Results: Of 230 pts in the MP OZA/OZA arm, 1 did not have post-BL PMS data available and was excluded from this analysis; 5 groups of pt-response patterns to OZA therapy were identified during MP. At W10, a PMS response was observed in all 5 trajectory groups (TGs). During the 42-wk MP, TGs diverged into fast sustained improvement (Group [G] 1; n=38 [16.6%, 38/229]); slow sustained improvement (G2; n=85 [37.1%, 85/229]); gradual improvement (G3; n=60 [26.2%, 60/229]); fast rebound (G4; n=25 [10.9%, 25/229]); and slow rebound (G5; n=21 [9.2%, 21/229]). All pts entering the MP were OZA clinical responders, but 20% of pts did not demonstrate sustained improvement from BL in PMS (G4 and G5); 80% demonstrated sustained improvement from BL in PMS (G1–3). From W10 onward, 26.2%, 37.1%, and 16.6% of pts achieved and maintained PMS reductions of ≥3.98, ≥5.27, and ≥6.71 points, respectively. Pts in G4 and G5 were slightly younger at diagnosis and had a higher W10 Geboes histologic index score vs the other TGs; pts in G4 had the most corticosteroid use at screening (Table 1). At W52, more pts in G1–3 combined achieved clinical response (74%) and clinical remission (46%) vs those in G4 and G5 combined (7% and 2%, respectively). G1–3 combined had more pts with endoscopic improvement (56%) and mucosal healing (37%) at W52 vs G4 and G5 combined (7% and 2%, respectively). Conclusion: Five groups of pt-response trajectories to OZA tx were identified; 80% of pts in G1–3 had sustained response to OZA tx. GBTM identified clinically meaningful pt subgroups by pt-response patterns to OZA tx. This approach needs to be validated in prospective studies. Table 1. - Pt characteristics at BL (TN W0) or W10 G1: Fast sustained improvement (n=38; 6.6% [38/229]) G2: Slow sustained improvement (n=85; 37.1% [85/229]) G3: Gradual improvement (n=60; 26.2% [60/229]) G4: Fast rebound (n=25; 10.9% [25/229]) G5: Slow rebound (n=21; 9.2% [21/229]) Sex, male, n (%) 15 (39.5) 43 (50.6) 33 (55.0) 13 (52.0) 12 (57.1) Age at UC diagnosis, y, mean (SD) 34.6 (12.4) 35.7 (14.1) 35.3 (13.0) 29.8 (11.5) 31.5 (11.0) Corticosteroid use at screening, n (%) 11 (28.9) 28 (32.9) 14 (23.3) 11 (44.0) 7 (33.3) Prior use of tumor necrosis factor antagonist, n (%) 9 (23.7) 28 (32.9) 22 (36.7) 9 (36.0) 7 (33.3) Complete Mayo score at W10, mean (SD) 2.8 (1.7) 3.5 (1.8) 3.8 (1.9) 4.8 (2.1) 3.7 (1.6) PMS at W10, mean (SD) 1.3 (1.0) 1.9 (1.2) 2.1 (1.4) 3.0 (1.8) 2.1 (1.2) Mucosal endoscopy subscore of 2 (moderate) at BL, n (%) 14 (36.8) 39 (45.9) 28 (46.7) 9 (36.0) 8 (37.1) Mucosal endoscopy subscore of 3 (severe) at BL, n (%) 24 (63.2) 46 (54.1) 32 (53.3) 16 (64.0) 13 (61.9) Geboes continuous index score at W10, mean (SD) 5.9 (4.3) 5.8 (4.9) 7.0 (5.2) 7.7 (5.1) 7.6 (4.8)
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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 | 0,005 | 0,007 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,002 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 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 ».