[炎症性肠病中的新旧生物制剂和小分子:抗整合素]。

Kyeong Ok Kim, Si Hyung Lee
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引用次数: 0

摘要

最近,一些新型生物制剂或小分子药物被引入炎症性肠病(IBD)治疗领域,以满足与抗肿瘤坏死因子α药物相关的未被满足的需求。在这些新型药物中,抗整合素药物通过阻断整合素与细胞粘附分子之间的相互作用,阻止白细胞向肠道迁移。Vedolizumab(抗α4β7)是目前应用最广泛的抗整合素药物,已被批准用于溃疡性结肠炎和克罗恩病的治疗。目前已开发出几种结合临床、遗传、免疫和肠道微生物标记物的模型,用于预测 IBD 患者对维多珠单抗的反应。Etrolizumab(抗β7)通过α4β7阻断白细胞迁移,通过αEβ7整合素阻断细胞粘附。此外,皮下注射维多珠单抗也显示出相似的疗效和安全性,并为患者提供了更多便利。其他正在研究的抗整合素疗法包括:abrilumab(抗α4β7 IgG2)、PN-943(口服肠道限制性α4β7拮抗剂肽)、AJM300(口服活性小分子α4抑制剂)和ontamalimab(抗MAdCAM-1 IgG)。
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[Old and New Biologics and Small Molecules in Inflammatory Bowel Disease: Anti Integrins].

Recently, novel biologics or small molecular drugs have been introduced for overcoming the unmet needs associated with anti-tumor necrosis factor α agents for inflammtory bowel disease (IBD) treatment. Among these novel drugs, anti integrin agents block leukocyte trafficking to the intestine by blocking the interaction between integrin and cell adhesion molecules. Vedolizumab (anti-α4β7) is most widely used anti-integrin approved in both ulcerative colitis and Crohn's disease .It has been shown to be effective in both induction and maintenance therapy with a favorable safety profile due to gut selectivity. Several models incorporating clinical, genetic, immune and gut microbial markers to predict response to vedolizumab in IBD have been developed. Etrolizumab (anti-β7) blocks leukocyte trafficking via α4β7 and cell adhesion via αEβ7 integrins. In addition, the introduction of subcutaneous vedolizumab showed similar efficacy and safety with improved patients' convenience. Other investigational anti-integrin therapies include abrilumab (anti-α4β7 IgG2), PN-943 (orally administered and gut-restricted α4β7 antagonist peptide), AJM300 (orally active small molecule inhibitor of α4), and ontamalimab (anti-MAdCAM-1 IgG).

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