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骨关节炎药物研发进展的现状:对当前挑战与未来机遇的全面叙述性综述

The current state of the osteoarthritis drug development pipeline: a comprehensive narrative review of the present challenges and future opportunities.

作者信息

Kim Heungdeok, Seo Jinwon, Lee Yunsin, Park Kiwon, Perry Thomas A, Arden Nigel K, Mobasheri Ali, Choi Heonsik

机构信息

Institute of Bio Innovation Research, Kolon Life Science, Inc., Seoul, South Korea.

Centre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.

出版信息

Ther Adv Musculoskelet Dis. 2022 Dec 7;14:1759720X221085952. doi: 10.1177/1759720X221085952. eCollection 2022.

Abstract

In this narrative review article, we critically assess the current state of the osteoarthritis (OA) drug development pipeline. We discuss the current state-of-the-art in relation to the development and evaluation of candidate disease-modifying OA drugs (DMOADs) and the limitations associated with the tools and methodologies that are used to assess outcomes in OA clinical trials. We focus on the definition of DMOADs, highlight the need for an updated definition in the form of a consensus statement from all the major stakeholders, including academia, industry, regulatory agencies, and patient organizations, and provide a summary of the results of recent clinical trials of novel DMOAD candidates. We propose that DMOADs should be more appropriately targeted and investigated according to the emerging clinical phenotypes and molecular endotypes of OA. Based on the findings from recent clinical trials, we propose key topics and directions for the development of future DMOADs.

摘要

在这篇叙述性综述文章中,我们批判性地评估了骨关节炎(OA)药物研发的现状。我们讨论了与候选疾病修饰性骨关节炎药物(DMOADs)的开发和评估相关的当前技术水平,以及用于评估OA临床试验结果的工具和方法所存在的局限性。我们聚焦于DMOADs的定义,强调需要由包括学术界、产业界、监管机构和患者组织在内的所有主要利益相关者以共识声明的形式给出更新的定义,并总结了新型DMOAD候选药物近期临床试验的结果。我们建议应根据OA新出现的临床表型和分子内型,更适当地靶向和研究DMOADs。基于近期临床试验的结果,我们提出了未来DMOADs开发的关键主题和方向。

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