DOP009 Effectiveness and Safety of Advanced Combination Treatment (ACT) in patients with refractory inflammatory bowel disease or concomitant immune mediated disease or extra-intestinal manifestations: A Multi-Center Canadian Study
Notice bibliographique
Résumé
Abstract Background Some patients with inflammatory bowel disease (IBD) do not respond to multiple advanced therapies, resulting in off-label use of two advanced therapeutic agents, known as advanced combination treatment (ACT) (1). Methods This multi-center study in 9 Canadian centers included adult IBD patients treated with either two biological therapies, a biological plus an oral small molecule, or two small molecules. The indication for ACT was characterized as: 1) refractory IBD; 2) concomitant uncontrolled IMID; 3) concomitant uncontrolled EIMs. Primary outcomes were cumulative rates of clinical and endoscopic response and remission at 12 months. Clinical activity was assessed using physician global assessments for both IBD and the concomitant IMID/EIMs. Secondary outcomes included serious adverse events and infections. Cox-proportional hazard analyses identified independent predictors of treatment effectiveness. Multivariate Imputation by Chained Equations accounted for missing data. Results We included 105 IBD patients (76 CD, 29 UC), median age 35 years (IQR 35.4-40.8). At baseline, 39% had perianal involvement, and 58% had failed at least 3 advanced therapies. Most patients (61%) had moderate to severe disease activity, and 40% had prior surgery. The cohort was categorized into three groups based on the rationale for ACT: 63.8% (67/105) received ACT for refractory IBD, 28.8% (30/105) for concomitant IMID, and 7.6% (8/105) for concomitant EIMs. The primary reason for ACT was refractory IBD (63.8%), with the add-on approach used in 97.1% combinations. The most frequent combination was anti-TNF + anti-integrin, followed by the combination of anti-IL-(12)/23 agent + anti-integrin. At 12 months, the cumulative rates of clinical and endoscopic response were 60% and 32.4%, respectively. Cumulative clinical and endoscopic remission rates were 29.5% and 28.6%, respectively (Table 1). Multivariate analysis showed perianal disease was associated with reduced chances of both clinical remission (HR = 0.33, p=0.001), and endoscopic remission (HR = 0.42, p=0.0001) (Table 2). Longer disease duration (HR = 0.96, p = 0.035), baseline moderate-severe disease (HR = 0.41, p = 0.026), and baseline steroid use (HR = 0.39, p = 0.006) were associated with a reduced likelihood of clinical remission. Serious adverse events and infections were reported in 12.4% and 7.6% of patients, respectively. Among serious infections, 5 (62.5%) required hospitalization, 3 (37.5%) were reported as important medical events, and none was life-threatening. Conclusion In this large real-world cohort, ACT was effective in achieving clinical and endoscopic outcomes in patients with refractory IBD or concomitant IMID/EIMs. ACT was well-tolerated, with a favorable safety profile. References 1. Danese S, Solitano V, Jairath V, Peyrin-Biroulet L. The future of drug development for inflammatory bowel disease: the need to ACT (advanced combination treatment). Gut. 2022 Dec;71(12):2380-2387. doi: 10.1136/gutjnl-2022-327025. Epub 2022 Jun 14. PMID: 35701092.
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 | 0,002 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| 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 ».