P472 Efficacy of intravenous ustekinumab re-induction in patients with Crohn’s disease with a loss of response
Notice bibliographique
Résumé
Ustekinumab (UST) has been shown to be effective in inducing and maintaining remission in patients with Crohn’s disease (CD). However, a significant number of patients do not respond or experience a secondary loss of response (LOR). We assessed the utility of UST intravenous (IV) re-induction (~6 mg/kg) to achieve clinical and endoscopic response or remission in patients with active CD on UST maintenance therapy. A multi-centre retrospective cohort study was performed. Adult patients (>18 years old) who received an IV re-induction dose of UST for either partial response or secondary LOR to UST, based on clinical, biochemical or endoscopic criteria, were identified at two Canadian academic centres. Post-reinduction, clinical remission was defined as an HBI < 5 off corticosteroids. Biochemical response and remission were defined as ≥ 50% decrease and normalisation, respectively, of faecal calprotectin (FCP) and/or CRP. Endoscopic remission was defined as a SES-CD score of < 3 and endoscopic response was defined as a decrease in SES-CD ≥ 50%. Adequate drug concentrations were defined as a UST level of ≥ 1 μg/ml. The primary outcome of interest was complete clinical, biochemical and endoscopic remission. Secondary outcomes included clinical remission, biomarker response, and safety. Twenty-eight patients (median age 35.5 years, 46% women) underwent IV reinduction between January 2017 and July 2018. The indication for re-induction was partial response in 43% (n = 12) and LOR in 57% (n = 16). The majority of patients (89%) received re-induction while receiving UST maintenance q 4 weeks. The median time to re-induction was 18.5 months (interquartile range [IQR]: 13.0–34.8). Clinical outcomes were assessed at a median of 14 weeks (IQR: 13–17) post re-induction. The primary outcome was achieved in 28.6% (n = 8). Clinical remission with biochemical response was achieved in 53.8% of patients (n = 14). Therapeutic drug monitoring for UST was performed in 10 patients prior to reinduction, and 18 patients post-reinduction. Pre-reinduction UST concentrations were ≥ 1 μg/ml (mean 3.8 ± 3.5 μg/ml) in 80%, compared with 100% of post-reinduction UST concentrations (mean 6.4 ± 4.2 μg/ml). The mean UST concentration post-reinduction was significantly higher in patients having achieved the primary outcome compared with those who did not (9.7 ± 4.1 vs. 4.8 ± 3.1 μg/ml, p = 0.01). No serious adverse events were reported following UST re-induction. Ustekinumab IV reinduction can be used safely to induce complete remission and response in patients with Crohn’s disease with partial response or losing response, even in the context of previously defined adequate UST drug concentrations. Further studies evaluating this strategy are warranted.
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 | 0,000 | 0,001 |
| 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 | 0,001 |
| 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 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 ».