Differential efficacy of medical therapies for ulcerative colitis according to disease extent: patient-level analysis from multiple randomized controlled trials
Notice bibliographique
Résumé
Background: Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to severely active UC vary according to disease extent at enrollment. Methods: We analyzed patient level data from 11 Phase 2 and 3 clinical trials of advanced therapies in patients with moderate-to-severe UC to assess modifications of advanced therapy effects by disease extent. Primary outcome was clinical response and secondary outcomes were clinical remission, endoscopic response/remission and endoscopic improvement, and Mayo clinic subscore for both induction and maintenance studies. Binary and continuous outcomes were analyzed using the modified Poisson regression model and the mixed-effects model, respectively, adjusting for age, sex, disease duration, concomitant steroid use and prior anti-TNF use. Effect modifications with binary outcomes were quantified by ratios of risk ratio for left-sided to that for extensive colitis while effect modifications with the Mayo subscores were quantified by differences of the differences between mean scores of the left-sided and extensive colitis. Results were presented with point estimates and 95% confidence intervals as well as p-values. Findings: Eleven clinical trials enrolling 5450 UC patients (infliximab = 2, adalimumab = 2, golimumab = 2, vedolizumab = 2, tofacitinib = 3) were included. In induction trials, there was evidence to suggest effect modification by disease extent for clinical response with tofacitinib (the ratio of RRs 0.67, 95% CI [0.45, 0.99], p = 0.049) and clinical remission with infliximab (ratio of RRs 0.33, 95% CI [0.13, 0.85], p = 0.020) favoring patients with extensive colitis. There was no evidence to suggest effect modification for endoscopic improvement and clinical outcomes. There was evidence to suggest effect modification by disease extent for clinical remission with tofacitinib (ratio of RRs 0.44, 95% CI [0.22, 0.89], p = 0.020) favoring patients with extensive colitis. For symptom subscores from the Mayo Clinic score, tofacitinib was associated with a greater reduction in both stool frequency (difference of differences 0.37, 95% CI [0.08, 0.65], p = 0.012) and rectal bleeding scores (difference of differences 0.25, 95% CI [0.03, 0.47], p = 0.026) in patients with extensive colitis compared to left sided. Interpretation: These findings underscore the possibility of differential efficacy of medical therapies according to disease distribution. These results warrant further exploration in forthcoming trials to better inform treatment strategies and consideration of disease distribution as a baseline stratification factor in clinical trials. Funding: This study did not receive any financial support.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,004 | 0,056 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,002 |
| 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) | 0,001 | 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 tête enseignante, 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 ».