中轴型脊柱关节炎的治疗——乌帕替尼的见解。

Management of Axial Spondyloarthritis - Insights into Upadacitinib.

机构信息

Rheumazentrum Ruhrgebiet and Ruhr University Bochum, Herne, Germany.

出版信息

Drug Des Devel Ther. 2022 Oct 19;16:3609-3620. doi: 10.2147/DDDT.S330413. eCollection 2022.

Abstract

Although the pathogenesis of spondyloarthritis (SpA) has still not been elucidated our options to treat SpA have definitely improved in the last decades. There are two main types of SpA: (i) axial spondyloarthritis (axSpA), also covering the classical ankylosing spondylitis (AS) which is largely equivalent to radiographic (r)-axSpA but different from non-radiographic (nr)-axSpA, and (ii) peripheral SpA (pSpA) also covering psoriatic arthritis (PsA) as the main subtype. The subtype nr-axSpA has historically developed because the approval of drugs for AS did not cover forms without structural changes in the sacroiliac joints which is mandatory in the 1984 New York criteria. The definitions for axSpA are based on the 2009 Assessments in AxSpA International Society (ASAS) classification criteria. Several biologic disease modifying anti-rheumatic drugs (bDMARDs) such as the tumor necrosis factor alpha inhibitors (TNFi) and the interleukin-17-inhibitors (IL-17i) are approved mostly for the whole spectrum of SpA including axSpA and PsA but L-17i does not work in inflammatory bowel disease (IBD). Targeted synthetic (ts) DMARDs cover mainly the janus kinase (JAK)-inhibitors which have recently been developed to inhibit inflammation in several rheumatic and other immune mediated diseases such as IBD. Indeed, the physiologic mechanism of JAK-mediated signal transduction has been recognized as an important target because the inhibition of its actions was shown to successfully work as a therapeutic mechanism. There are now 4 small molecule JAK inhibitors (JAKi) that currently play a role in rheumatology with variable selectivity for the four different JAK isoforms: tofacitinib, baricitinib, upadacitinib and filgotinib. In this review, we summarize current clinical trial data and evaluate the use of the JAK1 selective inhibitor upadacitinib in the treatment of axSpA, including nr-axSpA and r-axSpA. Even though the efficacy and safety of upadacitinib over shorter periods of time has been convincing to date, long-term trials are needed to fully establish its performance and also evaluate the safety at higher doses, and its use in PsA.

摘要

虽然脊柱关节炎(SpA)的发病机制尚未阐明,但在过去几十年中,我们治疗 SpA 的选择肯定有所改善。SpA 有两种主要类型:(i)中轴型 SpA(axSpA),还包括经典的强直性脊柱炎(AS),其在很大程度上等同于放射学(r)-axSpA,但与非放射学(nr)-axSpA 不同,以及(ii)外周型 SpA(pSpA),还包括银屑病关节炎(PsA)作为主要亚型。nr-axSpA 亚型的出现是因为 AS 药物的批准并未涵盖骶髂关节无结构改变的形式,而这在 1984 年的纽约标准中是强制性的。axSpA 的定义基于 2009 年国际 SpA 评估协会(ASAS)分类标准。几种生物疾病修饰抗风湿药物(bDMARDs),如肿瘤坏死因子-α抑制剂(TNFi)和白细胞介素-17 抑制剂(IL-17i),主要批准用于 SpA 的整个谱,包括 axSpA 和 PsA,但 L-17i 在炎症性肠病(IBD)中无效。靶向合成(ts)DMARDs 主要涵盖最近开发的 Janus 激酶(JAK)抑制剂,用于抑制几种风湿性和其他免疫介导的疾病,如 IBD 的炎症。事实上,JAK 介导的信号转导的生理机制已被认为是一个重要的靶点,因为其作用的抑制被证明是一种成功的治疗机制。目前有 4 种小分子 JAK 抑制剂(JAKi)在风湿病学中发挥作用,对四种不同的 JAK 亚型具有不同的选择性:托法替尼、巴瑞替尼、乌帕替尼和菲戈替尼。在这篇综述中,我们总结了目前的临床试验数据,并评估了 JAK1 选择性抑制剂乌帕替尼在 axSpA 治疗中的应用,包括 nr-axSpA 和 r-axSpA。尽管迄今为止,乌帕替尼在较短时间内的疗效和安全性令人信服,但仍需要进行长期试验来充分确定其性能,并评估更高剂量的安全性,以及其在 PsA 中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3188/9578786/2810ae1b32aa/DDDT-16-3609-g0001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索