The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions. In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide. We review novel biologic agents targeting the T-helper 17 axis, including therapies directed towards interleukin (IL)-17 (secukinumab, ixekizumab, bimekizumab), IL-17R (brodalumab), IL-12/23p40 (ustekinumab, briakinumab) and IL-23p19 (guselkumab, tildrakizumab, brazikumab, risankizumab, mirikizumab). We also present an overview of biologics active against type I and II interferons, including sifalumumab, rontalizumab, anifrolumab and fontolizumab. Emerging strategies to interfere with cellular adhesion processes involved in lymphocyte recruitment are discussed, including both integrin blockade (natalizumab, vedolizumab, etrolizumab) and sphingosine-1-phosphate receptor inhibition (fingolimod, ozanimod). We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib) and second-generation selective JAK inhibitors (decernotinib, filgotinib, upadacitinib). New biologics targeting B-cells (including ocrelizumab, veltuzumab, tabalumab and atacicept) and the development of novel strategies for regulatory T-cell modulation (including low-dose IL-2 therapy and Tregitopes) are also discussed. Finally, we explore recent biotechnological advances such as the development of bispecific antibodies (ABT-122, COVA322), and their application to the treatment of IMIDs.

中文翻译：

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免疫介导的炎症性疾病的新疗法：我们可以从它们在类风湿性关节炎、脊柱关节炎、系统性红斑狼疮、银屑病、克罗恩病和溃疡性结肠炎中的应用中学到什么？

在生物技术和疾病知识的进步推动下，过去三十年见证了我们针对免疫和炎症反应的特定元素的能力取得了显着进步。除了为免疫介导的炎症性疾病 (IMID) 提供卓越的治疗外，此类疗法还为研究这些疾病的潜在免疫病理学基础提供了无与伦比的机会。在这篇综述中，我们探讨了最近治疗 IMID 的方法以及它们提供的对病理学的见解。我们回顾了针对 T-helper 17 轴的新型生物制剂，包括针对白介素 (IL)-17（苏金单抗、ixekizumab、bimekizumab）、IL-17R（brodalumab）、IL-12/23p40（ustekinumab、briakinumab）和 IL 的疗法-23p19（guselkumab、tildrakizumab、brazikumab、risankizumab、mirikizumab）。我们还概述了对 I 型和 II 型干扰素具有活性的生物制剂，包括 sifalumumab、rontalizumab、anifrolumab 和 fontolizumab。讨论了干扰参与淋巴细胞募集的细胞粘附过程的新兴策略，包括整合素阻断（那他珠单抗、维多珠单抗、埃曲珠单抗）和 1-磷酸鞘氨醇受体抑制（芬戈莫德、奥扎莫德）。我们总结了 Janus 激酶 (JAK) 抑制剂在治疗 IMIDs 中的发展和近期应用，包括第一代泛 JAK 抑制剂（托法替尼、巴瑞克替尼、鲁索替尼、培非替尼）和第二代选择性 JAK 抑制剂（去塞诺替尼、菲戈替尼、乌帕替尼） ）。靶向 B 细胞的新生物制剂（包括 ocrelizumab、veltuzumab、还讨论了 tabalumab 和 atacicept）以及调节性 T 细胞调节的新策略（包括低剂量 IL-2 治疗和 Tregitopes）的开发。最后，我们探讨了最近的生物技术进展，例如双特异性抗体（ABT-122、COVA322）的开发，以及它们在治疗 IMID 中的应用。