水平扫描:炎症性肠病管理的新疗法和未来疗法

Aditi Kumar, Philip J Smith
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摘要

目前炎症性肠病(IBD)的主要治疗方式包括免疫调节剂(甲氨蝶呤和硫嘌呤)、生物制剂(最常用的是抗肿瘤坏死因子α (TNF-α))和其他单克隆抗体,如抗整合素和抗白细胞介素(IL-12/23)。虽然理想的治疗应该在疾病过程的早期开始,以避免复发和并发症,但主要的反复出现的问题仍然是原发性和继发性反应丧失,在为IBD患者开出的下一条治疗线的疗效方面,往往“收益递减”。其他问题包括长期风险因素,如恶性肿瘤和易受感染。最近,有大量新兴药物进入市场,这些药物对以前对多种药物无效的中重度疾病患者显示出有希望的疗效。本文将重点介绍这些新兴的治疗方法——本质上是“水平扫描”——包括抗黏附剂、细胞因子抑制剂、Janus激酶抑制剂、磷酸二酯酶抑制剂、鞘鞘醇-1磷酸受体调节剂和MicroRNA-124 (miR-124)上调剂。
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Horizon scanning: new and future therapies in the management of inflammatory bowel disease
The current mainstay treatment modalities for inflammatory bowel disease (IBD) include immunomodulators (methotrexate and thiopurines), biologics (antitumour necrosis factor alpha (TNF-α) being the most commonly used) and other monoclonal antibodies such as the anti-integrins and anti-interleukins (IL-12/23). While ideally treatment should be initiated early in the disease process to avoid relapses and complications, the major recurring issue continues to be primary and secondary loss of response, with often ‘diminishing returns’ in terms of efficacy for the next line of therapies prescribed for patients with IBD. Additional concerns include the long-term risk factors such as malignancy and susceptibility to infections. Recently, there has been an influx of new and emerging medications entering the market that are showing promising efficacy results in patients with moderate-to-severe disease who have previously failed to respond to multiple drugs. This review will focus on these novel and emerging therapies—in essence, ‘horizon scanning’—which includes the antiadhesion agents, cytokine inhibitors, Janus kinase inhibitors, phosphodiesterase inhibitors, sphingosine-1 phosphate receptor modulators and MicroRNA-124 (miR-124) upregulators.
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