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炎症性肠病中的精准医学

Precision Medicine in Inflammatory Bowel Diseases.

作者信息

Marafini Irene, Monteleone Giovanni

机构信息

Gastroenterology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.

出版信息

Front Pharmacol. 2021 Apr 13;12:653924. doi: 10.3389/fphar.2021.653924. eCollection 2021.

Abstract

During the last decades, a better understanding of the mechanisms sustaining the pathogenic process in inflammatory bowel diseases (IBD) has contributed to expand the therapeutic armamentarium for patients with these disorders. Alongside with traditional therapies, monoclonal antibodies against tumor necrosis factor-α, the interleukin (IL)-12/IL-23 p40 subunit and the α4β7 integrin, and tofacitinib, a small molecule inhibiting intracellular pathways downstream to cytokine receptors, have entered into the clinic. However, these drugs are not effective in all patients and some responders can lose response over time. Such a therapeutic failure is, at least in part, dependent on the fact that, in IBD, the tissue damage is driven by simultaneous activation of multiple and distinct immune-inflammatory signals and the detrimental mucosal immune response changes over time even in the same patient. Therefore, personalized approaches aimed at identifying which patient should be treated with a specific drug at a precise time point are worth pursuing. A such approach has the advantage to improve efficacy of the drug and limit adverse reactions, thereby improving quality of the life of the patients and reducing costs. In this review, we summarize all the available evidence about the possible role of precision medicine in IBD.

摘要

在过去几十年中,对维持炎症性肠病(IBD)致病过程机制的更深入理解有助于扩大针对这些疾病患者的治疗手段。除了传统疗法外,抗肿瘤坏死因子-α、白细胞介素(IL)-12/IL-23 p40亚基和α4β7整合素的单克隆抗体,以及抑制细胞因子受体下游细胞内途径的小分子药物托法替布,都已进入临床。然而,这些药物并非对所有患者都有效,一些有反应的患者可能会随着时间的推移失去反应。这种治疗失败至少部分取决于以下事实:在IBD中,组织损伤是由多种不同免疫炎症信号的同时激活驱动的,即使在同一患者中,有害的黏膜免疫反应也会随时间而变化。因此,旨在确定哪些患者应在精确的时间点使用特定药物进行治疗的个性化方法值得探索。这种方法具有提高药物疗效和限制不良反应的优势,从而改善患者的生活质量并降低成本。在本综述中,我们总结了关于精准医学在IBD中可能作用的所有现有证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b77/8076955/a465e417ae6c/fphar-12-653924-g001.jpg

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