Higashiyama Masaaki, Hokari Ryota
Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Digestion. 2023;104(1):74-81. doi: 10.1159/000527422. Epub 2022 Nov 10.
BACKGROUND: The specific etiopathogenesis of inflammatory bowel disease (IBD) is still unknown. Although the conventional anti-inflammatory or immunomodulatory drugs relatively nonspecific to pathogenesis have been quite useful in many cases, elucidating the pathogenesis has gradually facilitated developments of disease-specific therapies for refractory cases in the last 2 decades. SUMMARY: With a greater understanding of the multiple overactive signaling pathways of the gut mucosal immune response and enhanced leukocyte trafficking, several biological agents or small molecule drugs following the first novel biologic, anti-tumor necrosis factor α (anti-TNFα), have been developed against several modes of action including adhesion molecules, sphingosine-1-phospate receptors, cytokines (IL-12/23, TL1A, and IL-36), Janus kinase (JAK), and phosphodiesterase. Although preceding biological agents have dramatically changed the IBD treatment strategy, many patients still require alternative therapies due to failure or side effects. Newer treatments are now expected to be provided for better efficacy with an improved adverse event profile. In addition, translational studies have highlighted the new therapeutic concepts' potential, including modulation of host-microbiome interactions, stem therapy for perianal fistula, regulation of fibrosis, regulation of the gut-brain axis, and control of previously less targeted immune cells (B cells and innate lymphoid cells). This paper comprehensively reviewed not only the latest already or shortly available therapies but also emerging promising treatments that will be hopefully established in the future for IBD. KEY MESSAGES: Many kinds of new treatments are available, and promising treatments with new perspectives are expected to emerge for refractory IBD in the future.
背景:炎症性肠病(IBD)的具体发病机制仍不清楚。尽管传统的抗炎或免疫调节药物对发病机制相对非特异性,但在许多情况下已相当有用,在过去20年中,对发病机制的阐明逐渐促进了针对难治性病例的疾病特异性疗法的发展。 总结:随着对肠道黏膜免疫反应多种过度活跃信号通路的深入了解以及白细胞运输的增强,继首个新型生物制剂抗肿瘤坏死因子α(抗TNFα)之后,已经开发出几种生物制剂或小分子药物,其作用模式包括黏附分子、鞘氨醇-1-磷酸受体、细胞因子(IL-12/23、TL1A和IL-36)、Janus激酶(JAK)和磷酸二酯酶。尽管先前的生物制剂极大地改变了IBD的治疗策略,但许多患者仍因治疗失败或出现副作用而需要替代疗法。现在期望提供更新的治疗方法,以提高疗效并改善不良事件谱。此外,转化研究突出了新治疗概念的潜力,包括调节宿主-微生物群相互作用、肛周瘘管的干细胞治疗、纤维化调节、肠-脑轴调节以及控制以前较少靶向的免疫细胞(B细胞和先天淋巴细胞)。本文不仅全面回顾了最新的已上市或即将上市的疗法,还回顾了未来有望确立的新兴有前景的IBD治疗方法。 关键信息:有多种新的治疗方法可用,未来有望出现针对难治性IBD的具有新视角的有前景的治疗方法。
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