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治療免疫介導炎性疾病方法的研究進展


  治療免疫介導的炎性疾病的新療法:我們可以從類風溼性關節炎、脊柱關節炎、系統性紅斑狼瘡、銀屑病、克羅恩氏病和潰瘍性結腸炎中學到什麼?

  摘 要

  過去三十年來,我們以生物技術疾病知識的進步為推動力,針對特定的免疫發炎反應要素,取得了顯著的進展。除了為免疫介導的發炎疾病(IMIDs)提供更好的治療外,這類治療還為研究這些疾病的潛在免疫病理學基礎提供了無與倫比的機會。

  The past three decades have witnessed remarkable advances in our ability to target specifc elements of the immune and in?ammatory response, fuelled by advances in both biotechnology and disease knowledge.As well as providing superior treatments for immune-mediated in?ammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.


  在這篇綜述中,我們探討了IMID治療的最新方法以及他們提供的病理生物學的見解。 我們回顧了靶向(IL-17)(secukinumab,ixekizumab,bimekizumab)、IL-17R(brodalumab)、IL-12 / 23p40(ustekinumab,briakinumab)和IL -23p19(guselkumab,tildrakizumab,brazikumab,risankizumab,mirikizumab)的新的生物學藥物。我們還介紹了對I型和II型干擾素有效的生物製劑的概述,包括sifalumumab,rontalizumab,anifrolumab和fontolizumab。討論了干擾涉及淋巴細胞募集的細胞粘附過程的新興策略,包括整聯蛋白阻滯劑(那他珠單抗,vedolizumab,etrolizumab)和鞘氨醇-1-磷酸受體抑制劑(fngolimod,ozanimod)。我們總結了Janus激酶(JAK)抑制劑在IMIDs治療中的發展和最近的應用,包括第一代泛JAK抑制劑(tofacitinib,baricitinib,ruxolitinib,pefcitinib)和第二代選擇性JAK抑制劑(decernotinib,flgotinib,upadacitinib )。還討論了靶向B細胞(包括ocrelizumab,veltuzumab,tabalumab和atacicept)的新生物製劑和調節性T細胞調節(包括低劑量IL-2療法和Tregitopes)的新策略的開發。最後,我們探索最近的生物技術進展,如雙特異抗體(ABT-122,COVA322)的開發,以及它們在治療IMID中的應用。

  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 (fngolimod, ozanimod).We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including frst-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, pefcitinib) and second-generation selective JAK inhibitors (decernotinib, flgotinib, 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 bispecifc antibodies (ABT-122, COVA322), and their application to the treatment of IMIDs.



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