S826 Baseline and Early Predictors of Response to Risankizumab Induction and Maintenance Treatment in Patients With Moderate to Severe Crohn's Disease
Notice bibliographique
Résumé
Introduction: Pivotal phase 3 induction (ADVANCE and MOTIVATE) and maintenance (FORTIFY) studies established that treatment with risankizumab (RZB), a humanized monoclonal antibody with high specificity for the p19 subunit of interleukin-23, was superior to placebo for achieving clinical remission and endoscopic response in patients with moderate to severe Crohn's disease (CD). This exploratory analysis aimed to determine predictors of response to risankizumab induction and maintenance therapy. Methods: Pooled data from patients in the RZB 600 mg intravenous (IV) dosing groups in ADVANCE + MOTIVATE induction studies (n=527) and data from the RZB 360 mg subcutaneous (SC) dosing group in FORTIFY (n=141) were evaluated. Multivariate logistic regression models were used to determine predictors of clinical and endoscopic outcomes at Weeks 12 and 52. For FORTIFY, separate logistic regression models were used to access end-of-induction characteristics for the achievement of outcomes at Week 52. Results: Baseline characteristics found to be predictive of clinical and/or endoscopic outcomes at Week 12 and Week 52 are highlighted in the Table. Age and duration of disease were evaluated but were not predictive. Compared to patients with ileal disease, patients with colonic disease were more likely to achieve endoscopic endpoints at Week 12, while patients with ileal-colonic disease were more likely to achieve endoscopic response at Week 12; patients with either colonic or ileal-colonic disease were more likely to achieve endoscopic response at Week 52. Conversely, patients with prior bio-failure at BL were less likely to achieve endoscopic response at Week 12, and clinical and endoscopic responses at Week 52. Patients using corticosteroids at BL were less likely to achieve clinical endpoints at Weeks 12 and 52. Patients achieving clinical or endoscopic endpoints at Week 12 were more likely to achieve these endpoints at Week 52. Conclusion: For patients treated with risankizumab, baseline disease location predicted achievement of endoscopic responses, corticosteroid use predicted achievement of clinical endpoints, and prior bio-failure status predicted achievement of both clinical and endoscopic endpoints at Week 52. Notably, achievement of clinical or endoscopic outcomes after induction with risankizumab were associated with a higher likelihood of achieving long-term clinical and endoscopic outcomes. Table 1. - Induction Baseline Characteristics and FORTIFY Week 0 Clinical Outcomes as Predictors of Week 12 Response to Risankizumab Induction and Week 52 Response to Risankizumab Maintenance Dosing Week 12 SF/APS Clinical Remission RZB 600 mg IV Week 12 CDAI Clinical Remission RZB 600 mg IV Week 12 CDAI Clinical Response RZB 600 mg IV Week 12Endoscopic Response RZB 600 mg IV Week 12Endoscopic Remission RZB 600 mg IV Week 12Ulcer-free Endoscopy RZB 600 mg IV Week 52 SF/APS Clinical Remission RZB 360 mg SC Week 52 CDAI Clinical Remission RZB 360 mg SC Week 52 CDAI Clinical Response RZB 360 mg SC Week 52Endoscopic Response RZB 360 mg SC Week 52Endoscopic Remission RZB 360 mg SC Week 52Ulcer-free Endoscopy RZB 360 mg SC Induction Baseline Characteristics as Predictors of ResponseOdds Ratio [95% CI]P-value Colonic Disease Only 1.436 [0.766, 2.693]P=0.260 1.653 [0.883, 3.094]P=0.116 1.448 [0.774, 2.709]P=0.247 5.178 [2.411, 11.123] P< 0.001 3.077 [1.425, 6.644] P=0.004 3.393 [1.510, 7.624] P=0.003 0.654 [0.265, 1.614]P=0.357 0.886 [0.357, 2.203]P=0.795 0.938 [0.378, 2.328]P=0.890 4.909 [1.468, 16.410] P=0.010 2.135 [0.722, 6.317]P=0.170 2.428 [0.731, 8.060]P=0.147 Ileal-colonic Disease Only 0.751 [0.411, 1.370] P=0.350 0.821 [0.451, 1.492] P=0.517 0.906 [0.506, 1.622] P=0.739 2.880 [1.379, 6.017] P=0.005 1.262 [0.590, 2.702] P=0.548 0.767 [0.331, 1.775] P=0.535 0.634 [0.263, 1.529] P=0.311 1.032 [0.426, 2.503] P=0.944 0.806 [0.333, 1.952] P=0.632 4.351 [1.318, 14.366] P=0.016 1.826 [0.627, 5.321] P=0.270 2.018 [0.617, 6.602] P=0.246 Bio-Failure Status 0.675 [0.423, 1.076] P=0.098 0.789 [0.495, 1.258] P=0.320 0.867 [0.540, 1.393] P=0.556 0.438 [0.271, 0.709] P< 0.001 0.597 [0.352, 1.013] P=0.056 0.570 [0.317, 1.026] P=0.061 0.425 [0.229, 0.787] P=0.006 0.373 [0.200, 0.698] P=0.002 0.426 [0.225, 0.805] P=0.009 0.443 [0.233, 0.844] P=0.013 0.444 [0.228, 0.863] P=0.017 0.295 [0.144, 0.606] P< 0.001 Corticosteroid Use 0.506 [0.321, 0.799] P=0.003 0.491 [0.313, 0.769] P=0.002 0.440 [0.283, 0.683] P< 0.001 0.742 [0.466, 1.181] P=0.208 0.786 [0.463, 1.334] P=0.372 0.891 [0.493, 1.609] P=0.701 0.443 [0.243, 0.805] P=0.008 0.331 [0.178, 0.613] P< 0.001 0.374 [0.210, 0.668] P< 0.001 0.796 [0.430, 1.474] P=0.468 0.787 [0.403, 1.539] P=0.485 0.939 [0.450, 1.959] P=0.866 Induction Week 12 Clinical Outcomes as Predictors of Response at Maintenance Week 52Odds Ratio [95% CI]P-value SF/APS Clinical Response 1.538 [0.969, 2.442] P=0.068 1.418 [0.894, 2.249] P=0.137 1.596 [1.005, 2.535] P=0.048 2.880 [1.737, 4.774] P< 0.001 4.417 [2.466, 7.909] P< 0.001 3.517 [1.884, 6.565] P< 0.001 SF/APS Clinical Remission 2.084 [1.095, 3.967] P=0.025 1.429 [0.760, 2.684] P=0.268 1.704 [0.889, 3.267] P=0.109 3.696 [1.904, 7.172] P< 0.001 5.368 [2.542, 11.337] P< 0.001 5.091 [2.264, 11.448] P< 0.001 Endoscopic Response 1.066 [0.527, 2.156] P=0.860 0.886 [0.438, 1.793] P=0.736 1.279 [0.613, 2.666] P=0.512 3.592 [1.712, 7.540] P< 0.001 5.765 [2.663, 12.479] P< 0.001 6.314 [2.824, 14.120] P< 0.001 Endoscopic Remission 1.186 [0.503, 2.796] P=0.696 0.810 [0.344, 1.907] P=0.629 1.067 [0.433, 2.625] P=0.888 4.342 [1.732, 10.887] P=0.002 9.227 [3.436, 24.776] P< 0.001 8.036 [2.934, 22.006] P< 0.001
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 | 0,002 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| 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) | 0,002 | 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 ».