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转变风湿病临床试验:迈向以患者为中心的精准医学。

Transforming clinical trials in rheumatology: towards patient-centric precision medicine.

机构信息

Centre for Experimental Medicine & Rheumatology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

CREATE Centre, Section of Rheumatology, Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff University, Cardiff, UK.

出版信息

Nat Rev Rheumatol. 2020 Oct;16(10):590-599. doi: 10.1038/s41584-020-0491-4. Epub 2020 Sep 4.

Abstract

Despite the success of targeted therapies in the treatment of inflammatory arthritides, the lack of predictive biomarkers drives a 'trial and error' approach to treatment allocation, leading to variable and/or unsatisfactory responses. In-depth characterization of the synovial tissue in rheumatoid arthritis, as well as psoriatic arthritis and spondyloarthritis, is bringing new insights into the diverse cellular and molecular features of these diseases and their potential links with different clinical and treatment-response phenotypes. Such progress raises the tantalizing prospect of improving response rates by matching the use of specific agents to the cognate target pathways that might drive particular disease subtypes in specific patient groups. Innovative patient-centric, molecular pathology-driven clinical trial approaches are needed to achieve this goal. Whilst progress is clearly being made, it is important to emphasize that this field is still in its infancy and there are a number of potential barriers to realizing the premise of patient-centric clinical trials.

摘要

尽管靶向治疗在治疗炎性关节炎方面取得了成功,但缺乏预测生物标志物导致了治疗分配的“试错”方法,导致反应的可变性和/或不令人满意。对类风湿关节炎、银屑病关节炎和强直性脊柱炎的滑膜组织进行深入表征,为这些疾病的不同细胞和分子特征及其与不同临床和治疗反应表型的潜在联系提供了新的见解。这一进展提出了一个诱人的前景,即通过将特定药物与可能驱动特定患者群体中特定疾病亚型的同源靶途径相匹配,提高反应率。需要创新的以患者为中心、以分子病理学为驱动的临床试验方法来实现这一目标。虽然进展明显,但重要的是要强调,该领域仍处于起步阶段,实现以患者为中心的临床试验的前提存在许多潜在障碍。

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