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用于中重度活动性溃疡性结肠炎的白细胞介素23p19疗法。

IL23p19 therapies for moderately-to-severely active ulcerative colitis.

作者信息

Ahmed Newaz Shubidito, Ma Christopher

机构信息

Department of Medicine, University of Calgary, Calgary, AB, Canada.

Division of Gastroenterology & Hepatology, University of Calgary, Calgary, AB, Canada.

出版信息

Expert Opin Biol Ther. 2025 Apr;25(4):363-378. doi: 10.1080/14712598.2025.2480258. Epub 2025 Mar 24.

Abstract

INTRODUCTION

Ulcerative colitis (UC) is a chronic, relapsing and remitting, inflammatory bowel disease. Monoclonal antibodies targeting interleukin (IL)-23p19 have been developed to treat chronic inflammatory diseases mediated by aberrant IL23/Th17 responses, including psoriasis, psoriatic arthritis, and Crohn's disease. More recently, these agents have been evaluated for the treatment of moderately-to-severely active UC.

AREAS COVERED

In this review, we summarize and discuss phase 2 and pivotal phase 3 clinical trials informing the efficacy and safety of mirikizumab (AMAC, LUCENT, and SHINE), risankizumab (INSPIRE, COMMAND), and guselkumab (QUASAR, VEGA). The literature search included original research publications, secondary publications, and preliminary data from conference abstracts presented at international gastroenterology meetings from the past 5 years.

EXPERT OPINION

The approval of IL23p19 antagonists expands the armamentarium of effective and safe therapies for patients living with moderately-to-severely active UC. These agents demonstrate potent efficacy for both inducing and maintaining symptomatic and objective disease endpoints, including endoscopic, histologic, and biomarker remission. These well-tolerated agents are effective in both advanced treatment-naïve and experienced patients. Accordingly, IL23p19 antagonists have the potential to be used in a diverse population of patients with UC, and as potential platform therapies for future combinations with other targeted immunomodulatory agents.

摘要

引言

溃疡性结肠炎(UC)是一种慢性、复发缓解型炎症性肠病。已开发出靶向白细胞介素(IL)-23p19的单克隆抗体,用于治疗由异常IL23/Th17反应介导的慢性炎症性疾病,包括银屑病、银屑病关节炎和克罗恩病。最近,这些药物已被评估用于治疗中度至重度活动性UC。

涵盖领域

在本综述中,我们总结并讨论了2期和关键3期临床试验,这些试验为mirikizumab(AMAC、LUCENT和SHINE)、risankizumab(INSPIRE、COMMAND)和guselkumab(QUASAR、VEGA)的疗效和安全性提供了依据。文献检索包括原始研究出版物、二次出版物以及过去5年在国际胃肠病学会议上发表的会议摘要中的初步数据。

专家意见

IL23p19拮抗剂的获批扩大了用于中度至重度活动性UC患者的有效和安全治疗手段。这些药物在诱导和维持症状性及客观疾病终点方面显示出强大疗效,包括内镜、组织学和生物标志物缓解。这些耐受性良好的药物在初治和有治疗经验的晚期患者中均有效。因此,IL23p19拮抗剂有潜力用于不同人群的UC患者,并作为未来与其他靶向免疫调节剂联合使用的潜在平台疗法。

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