S747 Mirikizumab Improves Mental and Physical Health Outcomes in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies
Notice bibliographique
Résumé
Introduction: Mirikizumab (miri), an anti-IL-23p19 monoclonal antibody, demonstrated efficacy vs. placebo (PBO) in adult patients (pts) with moderately to severely active ulcerative colitis (UC) in phase 3, randomized, double-blind, PBO-controlled 12-week (W) induction (LUCENT-1/NCT03518086) and 40-W maintenance (LUCENT-2/NCT03524092) studies.1,2 Here we evaluated the effect of miri vs. PBO on Medical Outcomes Study 36-Item Short Form Health Survey (SF-36; version 2) scores. Methods: In the induction study, 1162 pts who had an inadequate response/loss of response/intolerance to conventional/biologic therapy were randomized (3:1) to receive miri 300 mg IV (N=868) or PBO (N=294) every 4 weeks (Q4W). Pts who achieved clinical response with miri at W12 in the induction study (miri clinical responders; N=544) were re-randomized (2:1) to miri 200 mg subcutaneous (N=365) or PBO (N=179) Q4W through W40 (i.e., W52 of continuous therapy) in the maintenance study. Least squares mean (LSM) change from baseline in physical (PCS) and mental (MCS) component scores, and 8 domain scores (physical functioning, role-physical, role-emotional, bodily pain, vitality, social functioning, mental and general health) of the SF-36 survey were evaluated at W12 and W40. Treatment comparisons were made using analysis of covariance. Results: During the induction period, significant improvements in PCS (LSM difference vs. PBO [95% CI]: 2.07 [1.21, 2.93]; p< 0.001) and MCS (1.60 [0.56, 2.63]; p=0.002), and all domain scores (p< 0.05) of SF-36 were achieved with miri vs. PBO at W12. These improvements in SF-36 scores were sustained throughout the maintenance period with significant improvements seen with miri vs. PBO group in PCS (2.30 [1.12, 3.49]; p< 0.001) and MCS (1.48 [0.13, 2.82]; p=0.031), and 6/8 domain scores (p< 0.05) at W40 (Table). Conclusion: Miri significantly improves SF-36 mental and physical component scores in patients with moderately to severely active UC during induction (W12) and maintenance (W40). Table 1. - Change From Baseline (ANCOVA with mBOCF*) in SF-36 Physical and Mental Component Scores and Domain Scores at W12 and W40 (Modified Intent-to-treat Population) Induction (W12 analysis) Maintenance (W40 analysis)Miri clinical responder LSM (SE) change from baseline † LSM Diff (95% CI) vs. PBO p-value LSM (SE) change from baseline † LSM Diff (95% CI) vs. PBO p-value PBO IV (N=294) Miri 300 mg IV (N=868) PBO SC (N=179) Miri 200 mg SC (N=365) PCS 3.90 (0.393) 5.97 (0.242) 2.07 (1.21, 2.93) < 0.001 6.66 (0.541) 8.97 (0.412) 2.30 (1.12, 3.49) < 0.001 MCS 3.42 (0.472) 5.02 (0.291) 1.60 (0.56, 2.63) 0.002 5.54 (0.611) 7.02 (0.465) 1.48 (0.13, 2.82) 0.031 Domain scores Physical Functioning 6.57 (0.950) 10.16 (0.585) 3.59 (1.51, 5.67) < 0.001 10.82 (1.221) 13.97 (0.928) 3.16 (0.48, 5.84) 0.021 Role-Physical 10.50 (1.304) 17.21 (0.803) 6.71 (3.86, 9.57) < 0.001 18.51 (1.667) 26.14 (1.266) 7.63 (3.97, 11.28) < 0.001 Role-Emotional 5.25 (1.135) 9.06 (0.701) 3.81 (1.33, 6.30) 0.003 10.35 (1.338) 12.95 (1.019) 2.60 (−0.34, 5.54) 0.083 Bodily Pain 13.40 (1.218) 18.43 (0.751) 5.03 (2.37, 7.70) < 0.001 20.93 (1.663) 26.12 (1.263) 5.19 (1.54, 8.84) 0.005 Vitality 10.38 (1.059) 14.72 (0.652) 4.34 (2.02, 6.65) < 0.001 16.85 (1.493) 21.54 (1.133) 4.70 (1.42, 7.97) 0.005 Social Functioning 11.69 (1.254) 16.74 (0.772) 5.05 (2.30, 7.79) < 0.001 17.25 (1.487) 23.95 (1.129) 6.70 (3.44, 9.96) < 0.001 Mental Health 6.55 (0.887) 9.56 (0.548) 3.00 (1.06, 4.94) 0.002 10.25 (1.233) 12.93 (0.940) 2.67 (−0.04, 5.38) 0.053 General Health 7.03 (0.959) 12.30 (0.592) 5.27 (3.17, 7.37) < 0.001 14.23 (1.362) 19.83 (1.035) 5.59 (2.61, 8.58) < 0.001 *Patients with missing values had their last value carried forward, with the exception that patients who discontinued due to an adverse event had their baseline value carried forward.†Baseline for both Induction and Maintenance is defined as the last non-missing assessment recorded on or prior to the date of the first study drug administration at Visit 1 of Induction.ANCOVA, analysis of covariance; CI, confidence interval; Diff, difference; IV, intravenous; LSM, least squares mean; MCS, mental component score; mBOCF, modified baseline observation carried forward; miri, mirikizumab; PBO, placebo; PCS, physical component score; SC, subcutaneous; SE, standard error; SF-36, medical outcomes study 36-Item short-form health survey; W, week.
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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 | 0,001 | 0,001 |
| 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 | 0,000 | 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) | 0,002 | 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 ».