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从基础到临床——白细胞介素 17 药物在类风湿关节炎中有作用吗?

From bench to bedside - is there a role of IL-17 drugs in rheumatoid arthritis?

机构信息

Department of Rheumatology, University Hospitals of Birmingham, Birmingham, UK.

Department of Medicine, Northampton General Hospital, Northampton, UK.

出版信息

Expert Opin Investig Drugs. 2024 Jun;33(6):591-600. doi: 10.1080/13543784.2024.2351505. Epub 2024 May 9.

Abstract

INTRODUCTION

IL-17 has been described as a pro-inflammatory cytokine that is relevant in the seronegative spondylarthritides with IL-17 targeted therapies being licensed for their treatment.There is evidence to demonstrate that IL-17 is found in RA joints and contributes to the pro-inflammatory cascade. This results in synovial hyperplasia and osteoclastogenesis thus causing joint destruction and bony erosions.

AREAS COVERED

This review article summarizes trials that have studied the use of IL-17 targeted therapies in RA patients who have failed conventional synthetic disease-modifying therapy (C-DMARDS) and biologic DMARDS.

EXPERT OPINION

The trials that have studied IL-17 inhibitors in RA patients have only shown a modest improvement in disease activity. In several trials, the primary endpoint was not achieved whilst in others, when comparing with existing licensed biologics for RA, did not demonstrate any superiority.Tissue Necrosis Factor-alpha (TNF-α) likely plays more of a pivotal role in the pathogenesis of RA with IL-17 having a synergistic effect. Therefore, in our opinion, IL-17 inhibitors as an independent therapy for RA are less likely to provide a cost-effective benefit. There may be scope to potentially combine it with TNF-α-inhibitors (TNF-i), but this requires further research especially with the potential concerns related to increased immunosuppression.

摘要

简介

IL-17 被描述为一种促炎细胞因子,与血清阴性脊柱关节病有关,针对 IL-17 的治疗方法已获得许可用于其治疗。有证据表明,IL-17 存在于 RA 关节中,并有助于促炎级联反应。这导致滑膜增生和破骨细胞形成,从而导致关节破坏和骨侵蚀。

涵盖领域

本文综述了研究 IL-17 靶向治疗在常规合成疾病修饰疗法(C-DMARDS)和生物 DMARD 治疗失败的 RA 患者中的应用的试验。

专家意见

研究 IL-17 抑制剂在 RA 患者中的试验仅显示疾病活动度有适度改善。在几项试验中,主要终点未达到,而在其他试验中,与 RA 的现有许可生物制剂相比,并未显示出任何优越性。肿瘤坏死因子-α(TNF-α)可能在 RA 的发病机制中发挥更关键的作用,而 IL-17 具有协同作用。因此,我们认为,IL-17 抑制剂作为 RA 的独立治疗方法不太可能提供具有成本效益的益处。有可能将其与 TNF-α 抑制剂(TNF-i)联合使用,但这需要进一步研究,特别是与潜在的免疫抑制增加相关的潜在问题。

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