Targeting the Interleukin 23 Pathway in Inflammatory Bowel Disease

被引：7
作者：
Bourgonje, Arno R. [1 ,2 ]
Ungaro, Ryan C. [1 ]
Mehandru, Saurabh [1 ,2 ]
Colombel, Jean-Frederic [1 ]
机构：
[1] Icahn Sch Med Mt Sinai, Henry D Janowitz Div Gastroenterol, Dept Med, Gustave L Levy Pl, New York, NY 10029 USA
[2] Icahn Sch Med Mt Sinai, Precis Immunol Inst, New York, NY USA
来源：
GASTROENTEROLOGY | 2025年 / 168卷 / 01期
关键词：
Inflammatory Bowel Disease; Crohn's Disease; Ul- cerative Colitis; IL23; p19; Inhibitors; Efficacy; Safety; Pharma-; codynamics; Pharmacokinetics; Combination Therapy; Positioning; GENOME-WIDE ASSOCIATION; MAINTENANCE THERAPY; ULCERATIVE-COLITIS; CROHNS-DISEASE; PEPTIDE ANTAGONIST; INDUCTION THERAPY; IL-23; RECEPTOR; DOUBLE-BLIND; EFFICACY; SAFETY;
D O I：
10.1053/j.gastro.2024.05.036
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
Interleukin (IL) 23, a member of the IL12 family of cytokines, maintains intestinal homeostasis, but is also implicated in the pathogenesis of inflammatory bowel diseases (IBDs). IL23 is a heterodimer composed of disulfide-linked p19 and p40 subunits. Humanized monoclonal antibodies selectively targeting the p19 subunit of IL23 are poised to become prominent drugs in IBDs. In this review, we discuss the pharmacodynamic and pharmacokinetic properties of the currently available IL23p19 inhibitors and discuss the mechanistic underpinnings of their therapeutic effects, including the mechanism of action, epitope affinity, potency, and downstream signaling. Furthermore, we address available data on the efficacy, safety, and tolerability of IL23p19 inhibitors in the treatment of IBDs and discuss important studies performed in other immune-mediated inflammatory diseases. Finally, we evaluate the potential for combining classes of biological therapies and provide future directions on the development of precision medicine-guided positioning of IL23p19 inhibitors in IBD.
引用
收藏
页码：29 / 52.e3
页数：27
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