DOP022 Tacrolimus suppositories as induction therapy for refractory ulcerative proctitis: a randomised controlled trial
Notice bibliographique
Résumé
The treatment of 5-ASA refractory ulcerative proctitis (UP) remains challenging. Previous studies have shown that topical tacrolimus is effective for the treatment of refractory UP. However, the efficacy of tacrolimus as induction therapy compared with topical corticosteroids is unknown. We conducted a multicentre double-blinded randomised controlled trial in7 hospitals (EUDRACT number: 2013-001259-11). We randomly allocated adult patients (patients) with refractory UP in a 1:1 ratio, using a sealed envelope method, to either tacrolimus 2 mg suppositories OD (TSP) or beclomethasone 3 mg suppositories OD (BSP). Primary outcome was combined clinical remission, defined as a Colitis Activity Index (CAI) ≤ 4 and endoscopic remission, defined as Mayo score of 0 after 4 weeks. Secondary outcomes included clinical response defined as a decrease of CAI ≥3 from baseline, endoscopic response defined as a decrease in Mayo score ≥1 and/or decrease ≥5 cm extend of inflammation, and safety. All analyses were intention to treat. Outcomes were compared using X2 test or Mann–Whitney U test as appropriate. Between February 2014 and November 2017, 88 patients were included (66% F, mean age 41.8 years (SD14), median disease duration 7.1 years [IQR 2.8–13.6]). After randomisation, 45 patients received TSP and 43 patients BSP. Concomitant treatments in 53 patients (60%) were comparable for TSP and BSP patients; 5-ASA 17 vs. 23; immunomodulators 12 vs. 5; biologics 5 vs. 4, respectively (p > 0.05). Primary outcome was achieved in 6/45 (13.3%) patients receiving TSP vs. 6/43 (13.9%) patients who received BSP (p = 0.93). Clinical remission rate at week 4 was similar between the TSP group (53.3%, n = 24) and BSP group (58.1% n = 25) (p = 0.35). Endoscopic remission at week 4 was achieved in 24.4% (n = 11) patients treated with TSP vs. 13.9% (n = 6) patients treated with BSP (p = 0.11). The secondary outcome clinical response was achieved in 64.4% (n = 29) TSP patients and in 67.4% (n = 29) BSP patients (p = 0.46). Endoscopic response was seen in 55.6% (n = 25) TSP patients vs. 58.1% (n = 25) BSP patients (p = 0.47). Adverse events were reported in 22 (48.8%) TSP patients vs. 13 (30.2%) BSP patients (p = 0.05). Serious adverse events occurred in five patients (3 TSP, p = 0.68). In patients with 5-ASA refractory UP efficacy of topical tacrolimus was not statistically different compared with beclomethasone for inducing combined clinical and endoscopic remission, despite the observation of a higher rate of endoscopic remission after topical TSP. No differences were observed in clinical and endoscopic response rates. Fewer adverse effects were observed in the BSP-treated patients. Overall, our results demonstrate that tacrolimus suppositories could be considered as an alternative induction strategy for refractory UP (ZonMw Grant 836011003).
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) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,004 | 0,002 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,003 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,011 | 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 ».