S1449 Long-Term Endoscopic and Histological Outcomes of Mirikizumab in Patients With Moderately to Severely Active Ulcerative Colitis With up to 3 Years of Treatment
Notice bibliographique
Résumé
Introduction: Mirikizumab (MIRI), achieved the primary endpoint of clinical remission (CR) and other key secondary outcomes, including endoscopic and histologic improvement and remission at week (W) 12 of LUCENT-1 induction trial (NCT03518086), W52 of LUCENT-2 maintenance trial (NCT03524092), and W104 of LUCENT-3 long-term (LT) extension study (NCT03519945) in patients (pts) with moderately to severely active ulcerative colitis (UC).1-4 Here we present the LT durable and sustained histological and endoscopic outcomes through 3 years and their association with quality of life. Methods: LUCENT-3 is an ongoing single-arm, open-label, LT extension phase 3 study evaluating the efficacy and safety of MIRI in pts who participated in LUCENT-1 and -2. For pts who achieved CR at W52 (clinical remitters), we evaluated the proportion who achieved histologic improvement or remission (HI or HR), endoscopic remission or normalization (ER or EN), histologic-endoscopic mucosal improvement or remission (HEMI or HEMR), alternate HEMR (aHEMR: Geboes score≤ 2B.0 plus Mayo ES=0) or CR at W152 and maintenance of these endpoints from W52 to W104, and W152. The relationship between clinical outcomes and Inflammatory Bowel Disease Questionnaire (IBDQ) remission (defined as IBDQ score ≥170) was assessed at W152. Results: With 3 years of continuous MIRI treatment, the proportion of pts achieving ER, HI, HR, HEMI, HEMR, EN, aHEMR, and CR at W152 were 82%, 75%, 71%, 71%, 70%, 47%, 44%, and 81%, respectively (observed data) (Figure 1A). Achieving these outcomes was associated with IBDQ remission (P < 0.001) (Figure 1B). The proportion of pts who maintained ER, HI, HR, HEMI, HEMR, and CR across W52, W104, and W152 were 75%, 58%, 48%, 54%, 45%, and 74% (observed data) (Figure 1C). Greater than 90% of patients who maintained these outcomes at all timepoints during 3 years with MIRI achieved IBDQ remission (Figure 1D). Conclusion: MIRI maintained endoscopic and histologic outcomes through an additional 2 years of continuous treatment among clinical remitters at W52 (3 years in total). The achievement of LT durable and sustained endoscopic and histologic outcomes with MIRI was strongly associated with IBDQ remission. References 1. D'Haens G, et al. Gastroenterology. 2022;162(Suppl_7):S214.2. Dubinsky MC, et al. Gastroenterology. 2022;162(7, Suppl_7):S1393-S1394.3. Magro F, et al. United European Gastroenterology J. 2023;11(Suppl_8).4. Sands BE, et al. Inflamm Bowel Dis. 2024;izae024.Figure 1.: Long-term durable and sustained histological and endoscopic outcomes through 3 years and their association with IBDQ remission. A. Proportion of patients on MIRI achieving ER, HI, HR, HEMI, HEMR, EN, aHEMR, and CR at W152 among clinical remitters at W52. B. Association between IBDQ remission and ER, HR, HEMR and ER at W152. C. Proportion of patients on MIRI maintaining ER, HI, HR, HEMI, HEMR and CR across W52, W104 and W152. D. Association between IBDQ remission at W152 and maintaining ER, HR, HEMR and CR with MIRI treatment across W52, W104 and W152. **P <0.01; ***P <0.001: Yes vs NO achieving the targeted endpoint. P-values on associations were estimated using the chi-squared test. Missing data were imputed using mNRI, in addition to the observed data. IBDQ remission was defined as IBDQ score ≥170. All time points refer to the total duration of continuous mirikizumab treatment. aHEMR=alternate HEMR (Geboes score≤ 2B.0 + Mayo ES=0); CI=confidence interval; CR=clinical remission (MMS SF=0 or SF=1 with ≥1-point decrease from baseline; RB=0; ES=0 or 1 [excluding friability]); EN=endoscopic normalization (Mayo ES=0); ER=endoscopic remission (Mayo ES = 0 or 1 [excluding friability]); ES= endoscopic score; HEMI=histologic-endoscopic mucosal improvement (Mayo ES=0 or 1 [excluding friability] + Geboes score≤ 3.1); HEMR=histologic-endoscopic mucosal remission (Mayo ES=0 or 1 [excluding friability] + Geboes score≤ 2B.0); HI=histologic improvement (Geboes score≤ 3.1); HR=histologic remission (Geboes score≤ 2B.0); IBDQ, Inflammatory Bowel Disease Questionnaire; MMS, Mayo Modified Score; mNRI, modified nonresponder imputation; N, number of participants in the analysis population; NA, not available; OC, observed case; RB, rectal bleeding; SF, stool frequency; W, Week.
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 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| 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 ».