OP36 Efficacy and safety of combination induction therapy with guselkumab and golimumab in participants with moderately-to-severely active Ulcerative Colitis: Results through week 12 of a phase 2a randomized, double-blind, active-controlled, parallel-group, multicenter, proof-of-concept study
Notice bibliographique
Résumé
Abstract Background Preclinical data from a murine model of acute colitis suggest that dual blockade of interleukin(IL)-23 and TNFα more effectively prevented the development of colonic inflammation than each monotherapy. Guselkumab(GUS), an IL-23p19 subunit antagonist, is being studied in inflammatory bowel disease. Golimumab(GOL), a TNFα antagonist, is approved for ulcerative colitis(UC). The objective of this study was to evaluate the efficacy and safety of combination induction therapy with GUS+GOL vs GUS or GOL alone in adults with moderately-to-severely active UC. Methods 214 patients(pts) naïve to TNFα antagonists and refractory or intolerant to conventional therapy(ie, immunomodulators and/or corticosteroids) were randomly assigned to receive GUS 200mg intravenous(IV) at weeks(wks) 0, 4, and 8(n=71); GOL 200mg subcutaneous(SC) at wk0 then 100mg SC at wks2, 6, and 10(n=72); or combination with GUS 200mg IV+GOL 200mg SC at wk0, GOL 100mg SC at wks2, 6, and 10, and GUS 200mg IV at wks4 and 8(n=71). The primary endpoint was clinical response at wk12; the major secondary endpoint was clinical remission at wk12. Other key endpoints were clinical remission based on the modified Mayo score (mMayo), symptomatic remission, endoscopic improvement, endoscopic normalization, histologic remission, composite histologic-endoscopic endpoints, and biomarker outcomes. Results Baseline disease characteristics were similar among groups(Table 1), however a greater proportion of pts in both monotherapy groups had pancolitis vs the combination group. A greater proportion of pts who received combination therapy achieved clinical response at wk12(83.1%) vs GUS(74.6%) or GOL(61.1%)(Table 2). Similarly, the proportion of pts who achieved clinical remission in the combination group(36.6%) was greater than that of monotherapy groups(21.1% and 22.2%, respectively). Clinical remission by mMayo score, endoscopic improvement, histologic remission, both histologic remission and endoscopic improvement, and biomarker normalization (calprotectin, CRP) rates at wk12 were also greater in the combination group vs GUS or GOL. Percentages of pts with endoscopic normalization and both histologic remission and endoscopic normalization were nearly double with combination therapy vs either monotherapy. Adverse event(AE), serious AE, and infection rates were comparable among treatment groups. One pt receiving combination therapy experienced a serious infection of influenza and sepsis. No deaths, malignancies, or TB cases were reported through wk12. Conclusion Combination induction treatment with GUS+GOL more effectively induced clinical response, clinical remission, and endoscopic improvement at wk12 than either monotherapy alone. AE rates were comparable among the treatment groups.
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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| 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) | 0,000 | 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 ».