Ustekinumab for the Treatment of Anti-TNF-resistant Crohnʼs Disease: The McGill Experience
Notice bibliographique
Résumé
Purpose: Ustekinumab is a fully human IgG1κ monoclonalantibody that blocks the biologic activity of interleukin-12/23 through their common p40 subunit. Ustekinumab has been approved for treatment of plaque psoriasis. It was demonstrated to be effective for induction and maintenance of clinical response in anti-TNF resistant Crohn's disease (CD). The aim of this study was to analyse a real-life experience with open-label use of ustekinumab in anti-TNF=resistant CD patients in a tertiary referral center setting. Methods: This was a retrospective observational study. Clinical response was defined by physician's global assessment combined with decision to continue therapy. Patients were followed for up to 12 (8.6± 6) months or until discontinuation of ustekinumab. Sixteen (88.9%) patients received a loading dose ranging from 45 mg at week 0 and 4-90 mg at weeks 0,1, and 2. Initial maintenance doses included: 90 mg q8 weeks - 11 (61.1%), 90 mg q4 weeks -4 (22.2%), 45 mg q12 weeks-2 (12.5%), and 90 mg q12- in 1 (6.2%) patient. The primary endpoint was clinical response by week 12. Results: Patient characteristics: 18 patients treated at the McGill University IBD Centers (February, 2011-December, 2012) were included. The demographic and clinical characteristics of the patients were as follows: male-50%, age-32.9 ±13.8 years, age of onset of disease - 20.3 ±12.6 years. The disease characteristics were as following: location- ileocolonic-72.3%, colonic - 27.7, perianal disease - 27.7%, disease phenotype - luminal -44.4%, penetrating -38.9%, stricturing - 16.7%. Five (27.7%) patients had undergone total colectomy and ileostomy prior to initiation of ustekinumab. Previous therapies included a thiopurine drug in 100%, infliximab-in 100%, adalimumab-in 87.5%, certolizumab- in 25%, and methotrexate in 77.2% of the patients. Eleven (61.1%) patients were steroid-dependent at the time of initiation of ustekinumab. Treatment outcomes: Clinical response by 12 weeks was achieved in 11 (61.1%) patients. Six (54.5%) of these patients were steroid-dependent at treatment onset, three (50%) were able to discontinue steroids, and three (50%) decreased their prednisone dose by 50%. One additional patient achieved a clinical response after 16 weeks. Eight patients with short-term response were followed for 6 months, and six (75%) maintained their response. Five (83.3%) patients with maintained clinical response at six months were steroid-free. Four (66.7%) patients were followed for 12 months, and all were still clinically responsive and steroid-free. Conclusion: In this cohort of severe anti-TNF resistant CD patients, initial response to subcutaneous ustekinumab resulted in clinical response in 61.1% of patients, with the majority of responders sustaining the benefit for 6-12 months.
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) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| 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 ».