St John's Institute of Dermatology.
Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
Br J Dermatol. 2024 Jun 20;191(1):14-23. doi: 10.1093/bjd/ljae080.
More severe atopic dermatitis and psoriasis are associated with a higher cumulative impact on quality of life, multimorbidity and healthcare costs. Proactive, early intervention in those most at risk of severe disease may reduce this cumulative burden and modify the disease trajectory to limit progression. The lack of reliable biomarkers for this at-risk group represents a barrier to such a paradigm shift in practice. To expedite discovery and validation, the BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) consortium (a large-scale European, interdisciplinary research initiative) has curated clinical and molecular data across diverse study designs and sources including cross-sectional and cohort studies (small-scale studies through to large multicentre registries), clinical trials, electronic health records and large-scale population-based biobanks. We map all dataset disease severity instruments and measures to three key domains (symptoms, inflammatory activity and disease course), and describe important codependencies and relationships across variables and domains. We prioritize definitions for more severe disease with reference to international consensus, reference standards and/or expert opinion. Key factors to consider when analysing datasets across these diverse study types include explicit early consideration of biomarker purpose and clinical context, candidate biomarkers associated with disease severity at a particular point in time and over time and how they are related, taking the stage of biomarker development into account when selecting disease severity measures for analyses, and validating biomarker associations with disease severity outcomes using both physician- and patient-reported measures and across domains. The outputs from this exercise will ensure coherence and focus across the BIOMAP consortium so that mechanistic insights and biomarkers are clinically relevant, patient-centric and more generalizable to current and future research efforts.
更严重的特应性皮炎和银屑病与更高的生活质量累积影响、多种合并症和医疗保健成本相关。对那些最有可能患有严重疾病的患者进行积极、早期的干预,可能会减轻这种累积负担,并改变疾病轨迹,限制疾病进展。对于这个高危人群,缺乏可靠的生物标志物是实践中这种范式转变的一个障碍。为了加快发现和验证,特应性皮炎和银屑病的生物标志物(BIOMAP)联盟(一个大型的欧洲跨学科研究计划)已经整理了不同研究设计和来源的临床和分子数据,包括横断面和队列研究(从小规模研究到大型多中心登记处)、临床试验、电子健康记录和大规模基于人群的生物库。我们将所有数据集的疾病严重程度评估工具和指标映射到三个关键领域(症状、炎症活动和疾病过程),并描述了变量和领域之间的重要相互依赖关系和关系。我们根据国际共识、参考标准和/或专家意见,优先定义更严重的疾病。在分析这些不同研究类型的数据集时,需要考虑的关键因素包括明确考虑生物标志物的目的和临床背景、与特定时间点和随时间推移的疾病严重程度相关的候选生物标志物,以及在选择用于分析的疾病严重程度指标时考虑生物标志物的发展阶段,以及使用医生和患者报告的措施和跨领域验证生物标志物与疾病严重程度结果的相关性。这项工作的产出将确保 BIOMAP 联盟的一致性和重点,以便机制见解和生物标志物具有临床相关性、以患者为中心,并且更能推广到当前和未来的研究工作中。