S723 Duration of Response to Ozanimod After Treatment Withdrawal: Results From the Phase 3 True North Study
Notice bibliographique
Résumé
Introduction: The phase 3 True North (TN) randomized trial demonstrated efficacy and safety of ozanimod (OZA) in patients (pts) with moderately to severely active ulcerative colitis (UC). Temporary discontinuation of UC treatment can occur in clinical practice. Understanding the duration of response after treatment discontinuation can assist in clinical decision making. This analysis examined time to loss of OZA response in pts who discontinued OZA and switched to placebo (PBO) in the TN maintenance period (MP). Methods: In TN, pts were randomized to once-daily oral OZA 0.92 mg or PBO or to open-label OZA during a 10-week induction period (IP). Pts with clinical response to OZA at Week 10 were rerandomized to OZA (OZA-OZA) or PBO (OZA-PBO) in the MP through Week 52. Disease relapse was defined as an increase in partial Mayo score (PMS) of ≥2 points vs Week 10 with absolute PMS ≥4, endoscopic subscore ≥2, and exclusion of other causes of increased disease activity unrelated to UC. A subanalysis compared outcomes in OZA-OZA and OZA-PBO pts who entered the MP after achieving clinical remission (CRM) or clinical response (CRS only, excluding pts in CRM) at Week 10. Results: In the TN MP, 230 pts continued OZA (CRM, n=82; CRS only, n=148) and 227 pts switched to PBO (CRM, n=79; CRS only, n=148). Baseline characteristics were generally similar between groups. Pts in CRS only at Week 10 had a numerically higher proportion with severe disease and prior immunosuppressive medication use vs CRM pts (Table). Differences in disease relapse between groups became apparent after MP Week 8, after which a significantly higher proportion of OZA-OZA pts were without relapse vs OZA-PBO pts (Figure). MP Week 42 Kaplan-Meier (KM) estimates of no relapse were 86.1% and 62.6% for OZA-OZA and OZA-PBO pts, respectively. Additionally, pts in CRM at Week 10 had higher rates of nonrelapse during the MP vs those in CRS only at MP entry. KM estimates of non-relapse at MP Week 42 were 67.9% and 59.7% in OZA-PBO pts with CRM and CRS, respectively, and 90.9% and 83.4% in OZA-OZA pts with CRM and CRS, respectively. Conclusion: This analysis shows that OZA is effective at preventing disease relapse over 42 weeks of maintenance treatment in pts who achieve clinical response at Week 10. These data show that OZA maintains disease control even in the event of temporary discontinuation. However, extended discontinuation should be minimized in clinical practice.Figure 1 Table 1. - Baseline characteristics in pts in CRM vs pts in CRS only at Week 10 Pts in CRM a at IP Week 10 Pts in CRS b only at IP Week 10 OZA-PBO (n=79) OZA-OZA (n=82) OZA-PBO (n=148) OZA-OZA (n=148) Age, years, mean ± SD 45.0 ± 13.5 42.7 ± 13.9 42.0 ± 13.8 42.3 ± 13.4 Males, n (%) 45 (57.0) 41 (50.0) 77 (52.0) 76 (51.4) Years since UC diagnosis, mean ± SD 7.3 ± 7.0 7.4 ± 7.2 7.2 ± 7.3 8.9 ± 7.4 Prior therapies, n (%) 5-ASA CS Immunomodulator Anti-TNF Non-anti-TNF biologic 75 (94.9)51 (64.6)24 (30.4)13 (16.5)3 (3.8) 81 (98.8)54 (65.9)26 (31.7)15 (18.3)9 (11.0) 146 (98.6)117 (79.1)61 (41.2)52 (35.1)30 (20.3) 146 (98.6)109 (73.6)63 (42.6)61 (41.2)33 (22.3) Complete Mayo score c >9, n (%) 12 (15.2) 19 (23.2) 51 (34.5) 76 (51.4) Mayo endoscopic score = 3 (severe), n (%) 22 (27.8) 25 (30.5) 94 (63.5) 107 (72.3) Fecal calprotectin, median IQR, mg/kg 1027.8 (295.0, 2689.3) 851.6 (251.4, 2694.6) 1085.2 (434.4, 2579.3) 1285.0 (486.5, 2673.4) All data are reported at IP baseline.aCRM was defined as complete Mayo score of ≤2 with no individual subscore of >1 point.bCRS was defined as decrease from baseline of ≥3 points and at least 30% in the complete Mayo score and a decrease of ≥1 in RBS or an absolute RBS of ≤1.cThe sum of the rectal bleeding subscore, stool frequency subscore, Physician’s Global Assessment subscore, and endoscopy subscore.ASA, aminosalicylic acid; CRM, clinical remission; CRS, clinical response; CS, corticosteroid; IP, induction period; SD, standard deviation; TNF, tumor necrosis factor.
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 | 0,002 |
| 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 | 0,001 | 0,001 |
| 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 ».