25 Efficacy of IL-12/23 and IL-23 Antagonists for Moderate to Severe Crohn’s Disease in Advanced Treatment Failure Populations: A Network Meta-Analysis
Notice bibliographique
Résumé
Background: Recent approvals of advanced therapies have broadened the treatment landscape for Crohn’s disease (CD), providing patients with more options. While earlier clinical trials often used responder re-randomization designs, some newer therapies have been evaluated in treat-through trials. Combining heterogenous trial designs violates core assumptions of transitivity in network meta-analysis (NMA) and may lead to biased comparative efficacy estimates, especially for therapies with long half-lives that may impact withdrawal to placebo response rates in maintenance. This study aimed to compare the efficacy of interleukin (IL)-23 and IL-12/23 inhibitors for the treatment of moderate to severe CD using NMA focused on treat-through trials in advanced treatment failure populations. Methods: Indirect estimates were produced between risankizumab (RZB) 600 mg intravenous (IV) at weeks 0, 4, and 8 followed by RZB 360 mg subcutaneous (SC) every 8 weeks (Q8W), guselkumab (GUS) 200 mg IV or 400 mg SC at weeks 0, 4, and 8 followed by GUS 100 mg SC Q8W (GUS100) or GUS 200 mg SC Q4W (GUS200), mirikizumab (MIR) 900 mg IV at weeks 0, 4, and 8 followed by MIRI 300 mg Q4W, and ustekinumab (UST) 6 mg/kg IV at week 0 followed by UST 90 mg Q8W. Outcomes evaluated included clinical remission (Crohn’s Disease Activity Index < 150), endoscopic response (≥50% reduction in Simple Endoscopic Score for CD [SES-CD] score from baseline), and endoscopic remission (SES-CD ≤4 and a ≥2-point reduction from baseline and no subscore >1 in any individual component) at approximately 1 year of treatment (48–52 weeks). The NMA was conducted in a Bayesian framework utilizing placebo as the primary reference comparator of the network; outcomes were modeled with a binomial likelihood and a risk difference (RD)-link function. A statistically significant difference between comparators was declared if the 95% credible intervals (CrI) between the 2 comparators excluded the null value on the RD scale (i.e., RD of 0). Both fixed effects and random effects models were produced, with fixed effects models selected on the basis of parsimony. Results: All assessed therapies demonstrated a significantly greater RD across all outcomes relative to placebo, with RZB demonstrating the highest RD compared to placebo (clinical remission: 0.520 [95% CrI: 0.398, 0.639]; endoscopic response: 0.549 [0.438, 0.659]; endoscopic remission: 0.317 [0.223, 0.413]). The RDs in clinical remission for RZB (0.199 [0.114, 0.282]), GUS200 (0.141 [0.045, 0.235]), and GUS100 (0.108 [0.013, 0.201]) were significant relative to UST. For endoscopic response, the RD for RZB was significant relative to GUS100 (0.141 [0.022, 0.259]), MIRI (0.172 [0.052, 0.292]), and UST (0.230 [0.151, 0.308]). Additionally, the RDs for GUS200 (0.166 [0.074, 0.256]) and GUS100 (0.090 [0.001, 0.179]) were significant relative to UST. For endoscopic remission, the RD for RZB was significant relative to MIRI (0.112 [0.008, 0.218]) and UST (0.154 [0.082, 0.226]); the RD for GUS200 was significant relative to UST (0.117 [0.037, 0.197]). Conclusions: In this NMA of IL-23 and IL-12/23 inhibitors for moderate to severe CD in advanced treatment failure populations, RZB demonstrated the highest RD of achieving the evaluated outcomes compared to other IL-23 and IL-12/23 inhibitors.
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 | 0,044 | 0,052 |
| Méta-épidémiologie (sens strict) | 0,004 | 0,002 |
| Méta-épidémiologie (sens large) | 0,013 | 0,068 |
| Bibliométrie | 0,006 | 0,005 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,003 | 0,002 |
| Science ouverte | 0,003 | 0,003 |
| Intégrité de la recherche | 0,002 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».