Hiel Marjolein A J, Korte Eva W H, Tedbirt Billal, Bolling Marieke C, Meijer Joost M, Spuls Phyllis I, van der Werf Sjoukje, Yale Marc, Horváth Barbara, Joly Pascal
Department of Dermatology, Centre of Expertise for Blistering Diseases, European Reference Network for Rare Skin Diseases (ERN SKIN), University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
Department of Dermatology, Rouen University Hospital, Normandie university, and INSERM U1234, European Reference Network for Rare Skin Diseases (ERN SKIN), Centre de Reference des maladies bulleuses autoimmunes, Rouen, France.
Br J Dermatol. 2025 Apr 18. doi: 10.1093/bjd/ljaf152.
Pemphigus is an autoimmune bullous disease (AIBD) and has two main subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). For adequate interpretation and comparison of clinical studies in pemphigus, it is essential to have outcomes and outcome measurement instruments (OMIs) that are well-defined, uniform, and relevant.
To provide a comprehensive overview of previously reported outcomes and OMIs in pemphigus clinical research over the past two decades.
A systematic literature search was performed in the databases MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane CENTRAL, Web of Science and trial registries covering the period between January 2002 and December 2023. Clinical trials, prospective cohort studies and systematic reviews were included. Retrospective studies were excluded. All identified outcomes and their respective OMIs were grouped into outcome domains and areas.
From all the included studies (n=205), a total of 1,502 outcomes were extracted verbatim, categorized in 55 outcome domains and 11 outcome areas. We found a gradual increase in the number of published trials over the past two decades. The included studies mainly focused on "clinical response" (92%), "safety monitoring" (75%) and "immune response" (61%). "Quality of life" was sparsely reported (12%). Heterogeneity of reported outcomes was observed across all study designs. Within the outcome area "clinical response", the proportion of defined outcomes based on the 2008 consensus statement has not been consistent over time. However, four recent clinical trials used primary endpoints based on the 2008 consensus definitions. Moreover, a broad spectrum of outcome measurement instruments (n=65) was reported.
This review showed a wide variety in reported outcomes and OMIs in pemphigus clinical research over the past two decades. Despite standardization efforts, most studies still lack well-defined, consistent, and relevant outcomes and OMIs. However, a positive trend is emerging as four recent trials did use consensus-based definitions and patient-focused OMIs. Nevertheless, the outcomes are overly stringent, lack patient-centeredness, and do not include intermediate endpoints. Therefore, refinement of the 2008 expert consensus statement through collaborative efforts of all stakeholders is essential to promote uniformity in future pemphigus outcome measurement and advancing pemphigus drug development.
天疱疮是一种自身免疫性大疱性疾病（AIBD），主要有两种亚型：寻常型天疱疮（PV）和落叶型天疱疮（PF）。为了充分解读和比较天疱疮的临床研究，拥有定义明确、统一且相关的结局指标和结局测量工具（OMIs）至关重要。
全面概述过去二十年天疱疮临床研究中先前报道的结局指标和OMIs。
在MEDLINE、EMBASE、CINAHL、PsycINFO、Cochrane CENTRAL、Web of Science数据库以及试验注册库中进行系统文献检索，检索时间范围为2002年1月至2023年12月。纳入临床试验、前瞻性队列研究和系统评价。排除回顾性研究。所有识别出的结局指标及其各自的OMIs被归类为结局领域和范畴。
从所有纳入研究（n = 205）中，逐字提取了总共1502个结局指标，分为55个结局领域和11个结局范畴。我们发现过去二十年发表的试验数量逐渐增加。纳入研究主要集中在“临床反应”（92%）、“安全性监测”（75%）和“免疫反应”（61%）。“生活质量”的报道较少（12%）。在所有研究设计中均观察到所报道结局指标的异质性。在“临床反应”结局范畴内，基于2008年共识声明的定义结局指标的比例随时间并不一致。然而，最近的四项临床试验使用了基于2008年共识定义的主要终点。此外，还报道了广泛的结局测量工具（n = 65）。
本综述显示，在过去二十年的天疱疮临床研究中，所报道的结局指标和OMIs存在很大差异。尽管进行了标准化努力，但大多数研究仍然缺乏定义明确、一致且相关的结局指标和OMIs。然而，出现了一个积极趋势，即最近的四项试验确实使用了基于共识的定义和以患者为中心的OMIs。尽管如此，这些结局指标过于严格，缺乏以患者为中心，且未包括中间终点。因此，所有利益相关者共同努力完善2008年专家共识声明对于促进未来天疱疮结局测量的一致性和推进天疱疮药物研发至关重要。
