DOP74 Effectiveness of dose escalation in Crohn’s disease patients with insufficient response to standard-dose subcutaneous ustekinumab maintenance therapy: A multicentre international cohort study
Notice bibliographique
Résumé
Abstract Background Ustekinumab (UST) is an effective agent for induction and maintenance of response and remission in Crohn’s disease (CD). In addition to randomised controlled trials, an abundance of real-world evidence is available as well, suggesting that a substantial proportion of patients will not respond or lose response to UST therapy. To date, there is very little evidence to support the effectiveness of dose-optimisation strategy to manage primary or secondary non-response to ustekinumab. Methods This was a multicentre retrospective cohort study. The protocol was reviewed and approved by the Clinical Committee of ECCO. We included active (HBI≥5; CDAI ≥220) CD patients that received a standard-dose IV induction and at least one SC UST dose of 90 mg. Patients with ostomy were excluded. All patients received dose escalation by either shortening the interval between the doses to q4/6 weeks, intravenous reinduction or a combination of intravenous and subcutaneous escalation. The primary aim of the study was a clinical response (defined as Δ HBI≥3 or Δ CDAI ≥ 70 points) at week 16 after dose escalation. Clinical remission was defined as HBI<5 or CDAI <150. Results Of 140 patients, 83 (59.3%) were females, median age at treatment onset 36 (26–50) years, median duration of disease 9 (5–18) years from 21 centres in 13 countries (12 Europe, 1 Canada) were included. The patients were dose-escalated after a median treatment duration of 30 (20–45) weeks. Thirty-four (24,3%) were previously escalated from q12 to q8 maintenance regimen. Eighty-nine (63.5%) of the patients were escalated from q8 to q4 regimen, 20 (14.3%) – from q8 to q6, 15 (10.7%) received intravenous reinduction and 16 (11.4%) – a combination of intravenous reinduction and subcutaneous dose interval shortening. At week 16 from escalation, 83 (59.3%) responded to treatment, of them 21 (15%) were in clinical remission. Thirty-three (23.6%) of the patients were on systemic corticosteroids upon escalation; 7/33 (21.2%) achieved corticosteroid-free remission at week 16. One hundred and nine patients (77.8%) continued treatment beyond week 16. Follow-up data beyond week 16 were available for 75/150 (53.6%) of the patients (median duration of follow-up: 35 (32–54) weeks) from dose escalation. At the last follow-up, 53/75 (70.7%) continued to respond to treatment, including 42 (56%) in clinical remission; 25/75 (33%) discontinued treatment at last follow-up. Conclusion This large multicentre retrospective study demonstrates that intensification of ustekinumab maintenance dosage may be effective in up to 60% of the patients. This strategy should be considered in patients that are non-responsive to q8 ustekinumab maintenance dosing.
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 | 0,002 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».