P0608 Safety of guselkumab in Inflammatory Bowel Disease up to 1 year: Integrated safety analysis of phase 2 and 3 studies in Crohn’s Disease and Ulcerative Colitis
Notice bibliographique
Résumé
Abstract Background Guselkumab (GUS), a dual-acting IL-23 inhibitor that potently neutralizes IL-23 and binds to CD64 (a receptor on cells that produce IL-23), is currently approved in the United States for treatment of ulcerative colitis (UC) and worldwide for the treatment of plaque psoriasis and psoriatic arthritis. While GUS has been shown to be safe in Crohn’s disease (CD) and UC, safety results have only been reported in individual trials to date. To characterize the overall safety profile of GUS in inflammatory bowel disease (IBD), we evaluated pooled safety data from Phase 2/3 clinical trials of GUS in CD and UC. Methods Participants (pts) with moderately to severely active CD (n=1492; GALAXI 1, 2, and 3, and GRAVITI) or UC (n=1514; QUASAR Induction Study 1, Induction Study 2, and Maintenance Study and VEGA-GUS monotherapy arm only) were assigned to GUS 200 mg intravenous (IV) or 400 mg subcutaneous (SC) induction (GRAVITI only) at Weeks 0, 4, and 8, followed by GUS 100 mg SC every 8 weeks or 200 mg SC every 4 weeks; or placebo (PBO). SC maintenance treatment continued through approximately 1 year. GUS studies were pooled for the induction period (GALAXI, GRAVITI, and QUASAR; IV and SC, Weeks 0-12 [VEGA excluded due to no PBO control]) and through 1 year (GALAXI, GRAVITI, QUASAR, and VEGA). In this pooled analysis, safety events were normalized to 100 pt-years (PY) of follow-up with corresponding confidence intervals. Results Through Week 12, 1703 pts were treated with GUS with 399.9 PY of follow-up. Rates of adverse events (AEs) were similar between pts treated with GUS (200 mg IV or 400 mg SC) and PBO (Figure 1A). AEs occurred at a rate of 202.82/100 PYs and 223.26/100 PY, serious AEs at 11.75/100 PY and 28.56/100 PY, AEs leading to study agent discontinuation at 5.50/100 PY and 16.32/100 PY, and serious infections at 1.50/100 PY and 1.17/100 PY, for GUS and PBO, respectively. Through 1 year, 2057 pts were treated with GUS, with 1752.1 PY of follow-up. Rates of AEs, SAEs, AEs leading to discontinuation, and serious infections, were no higher in GUS-treated than PBO-treated pts (Figure 1B). Through 1 year, no anaphylactic or serum sickness reactions were reported, and rates of malignancy, opportunistic infection, major adverse cardiovascular events, and clinically important hepatic disorders were low (Table 1). In GUS-treated pts, one pt (from an endemic region) reported active tuberculosis, and 2 deaths (acute myocardial infarction in a pt with pre-existing cardiovascular risk factors and non-suicidal gunshot wound, respectively) occurred. Conclusion Through 1 year of treatment, GUS demonstrated a favorable safety profile comparable to placebo in patients with CD and UC. No new safety concerns were identified.
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 | 0,031 | 0,018 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,003 | 0,007 |
| Bibliométrie | 0,002 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
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 ».