无论基线改良梅奥评分如何，mirikizumab治疗中度至重度活动性溃疡性结肠炎的疗效和安全性：3期LUCENT试验结果

Efficacy and Safety of Mirikizumab in the Treatment of Moderately to Severely Active Ulcerative Colitis Regardless of Baseline Modified Mayo Score: Results From the Phase 3 LUCENT Trials.

作者信息

Abraham Bincy, Wu Jianmin, Vermeire Séverine, Melmed Gil, Ungaro Ryan, Charabaty Aline, Moses Richard, Chan-Diehl Faye, Paulissen Jerome, Zhu Baojin, Barnes Edward L, Ehrlich Adam C, Rubin David T

机构信息

Department of Medicine, Houston Methodist, Houston, TX, USA.

Eli Lilly and Company, Indianapolis, IN, USA.

出版信息

Crohns Colitis 360. 2025 Jan 8;7(2):otaf002. doi: 10.1093/crocol/otaf002. eCollection 2025 Apr.

DOI:10.1093/crocol/otaf002

PMID:40260308

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12010086/

Abstract

BACKGROUND

The modified Mayo score (mMS) is a measure for ulcerative colitis (UC) disease activity. Recent US Food and Drug Administration guidance for moderately to severely active UC trials suggests that patients should have baseline mMS of 5-9 including an endoscopy score of at least 2, as opposed to the previous range of 4-9. This disclosure reports results from patients with UC with baseline mMS of 5-9 who received mirikizumab, a monoclonal antibody directed against the interleukin-23 p19 subunit, or placebo in the phase 3 LUCENT trials.

METHODS

Mirikizumab was evaluated in the randomized, double-blind, placebo-controlled LUCENT-1 (NCT03518086) and LUCENT-2 (NCT03524092) trials, and the ongoing long-term LUCENT-3 (NCT03519945) trial, which use mMS 4-9. Analyses for patients with baseline mMS of 5-9 (excluding patients with mMS of 4) were conducted according to LUCENT trial statistical analysis plans. Categorical efficacy endpoints were summarized using proportions and confidence intervals. Continuous efficacy endpoints are presented as least-squares mean (standard error) changes from baseline.

RESULTS

Mirikizumab demonstrated efficacy for the primary endpoint of clinical remission and major secondary endpoints including clinical response, endoscopic improvement, histologic-endoscopic mucosal improvement/remission, bowel urgency remission, and corticosteroid-free remission. Importantly, mirikizumab exhibited greater improvements versus placebo in the Inflammatory Bowel Disease Questionnaire, fatigue, symptomatic remission, and work productivity. Finally, mirikizumab demonstrated long-term (104-week) sustained, durable efficacy across all studied endpoints. No new safety signals were identified during the 2-year follow-up.

CONCLUSIONS

Mirikizumab delivered significant clinical benefit for patients with baseline mMS of 5-9 and demonstrated a favorable safety profile.

摘要

背景

改良梅奥评分（mMS）是衡量溃疡性结肠炎（UC）疾病活动度的指标。美国食品药品监督管理局近期针对中度至重度活动性UC试验的指南建议，患者的基线mMS应为5 - 9，包括内镜评分至少为2，而之前的范围是4 - 9。本披露报告了在3期LUCENT试验中，基线mMS为5 - 9的UC患者接受抗白细胞介素-23 p19亚基单克隆抗体mirikizumab或安慰剂后的结果。

方法

在随机、双盲、安慰剂对照的LUCENT - 1（NCT03518086）和LUCENT - 2（NCT03524092）试验以及正在进行的长期LUCENT - 3（NCT03519945）试验中对mirikizumab进行了评估，这些试验使用的是mMS 4 - 9。根据LUCENT试验统计分析计划，对基线mMS为5 - 9（不包括mMS为4的患者）的患者进行了分析。分类疗效终点采用比例和置信区间进行总结。连续疗效终点以相对于基线的最小二乘均值（标准误差）变化表示。

结果

Mirikizumab在临床缓解的主要终点以及包括临床反应、内镜改善、组织学 - 内镜黏膜改善/缓解、肠道急迫缓解和无皮质类固醇缓解等主要次要终点方面均显示出疗效。重要的是，在炎症性肠病问卷、疲劳、症状缓解和工作生产力方面，mirikizumab相对于安慰剂表现出更大的改善。最后，mirikizumab在所有研究终点均显示出长期（104周）持续、持久的疗效。在2年随访期间未发现新的安全信号。