Yang Bingyi, Chen Yiran, Jiang Jiao, Chang Christopher, Wu Haijing, Gershwin M Eric, Lu Qianjin
Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, China.
Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China.
Clin Rheumatol. 2025 Jan;44(1):183-192. doi: 10.1007/s10067-024-07236-4. Epub 2024 Nov 23.
To evaluate the current usage of reproducible primary endpoints and tools for assessing treatment response for clinical trials for systemic lupus erythematosus (SLE), and emphasize the need for developing standardized, reproducible endpoints in this context.
A comprehensive review of Phase II and III SLE biologic trials from the past 15 years was conducted using PubMed and ClinicalTrials.gov. The analysis focused on clinical trial endpoints, disease activity indices, and the evolution of primary endpoints. Key measurement tools, including the British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA), the Systemic Lupus Erythematosus Responder Index (SRI), and the Systemic Lupus Activity Measure-Revised (SLAM-R), were examined.
The SRI emerged as the most commonly used composite measure for phase II/III clinical trial endpoints, with over 60% of ongoing trials employing SRI (4) as the primary endpoint. BICLA, derived from the British Isles Lupus Assessment Group (BILAG) index, was also frequently used but demonstrated notable differences from SRI in its approach. Our analysis underscores the ongoing need for more effective tools to assess disease activity and treatment response in SLE trials.
The selection of optimal primary endpoints is vital for SLE clinical trials due to the disease's heterogeneity and the variability in treatment responses. Currently, different primary endpoints are employed depending on the specific focus of clinical trials. While the SRI is widely used in phase II/III trials, the standardized efficacy measures are critical to enhancing the design and outcomes of future SLE clinical trials. Key points • Selecting optimal primary endpoints is crucial for SLE clinical trials. • Challenges in SLE treatment response assessment include patient heterogeneity and inconsistent disease activity evaluation. • BICLA and SRI are commonly used as primary endpoints but have notable differences. • There is an urgent need for better tools to assess disease activity and response in SLE clinical trials.
评估目前可重复的主要终点指标及用于评估系统性红斑狼疮（SLE）临床试验治疗反应的工具的使用情况，并强调在此背景下开发标准化、可重复终点指标的必要性。
使用PubMed和ClinicalTrials.gov对过去15年的II期和III期SLE生物制剂试验进行全面回顾。分析聚焦于临床试验终点指标、疾病活动指数以及主要终点指标的演变。对关键测量工具进行了检查，包括基于不列颠群岛狼疮评估组的综合狼疮评估（BICLA）、系统性红斑狼疮反应指数（SRI）和修订后的系统性狼疮活动度量表（SLAM-R）。
SRI成为II期/III期临床试验终点指标中最常用的综合指标，超过60%的正在进行的试验采用SRI（4）作为主要终点指标。源自不列颠群岛狼疮评估组（BILAG）指数的BICLA也经常被使用，但在方法上与SRI存在显著差异。我们的分析强调了在SLE试验中持续需要更有效的工具来评估疾病活动和治疗反应。
由于SLE疾病的异质性和治疗反应的变异性，选择最佳主要终点指标对SLE临床试验至关重要。目前，根据临床试验的具体重点采用不同的主要终点指标。虽然SRI在II期/III期试验中广泛使用，但标准化疗效指标对于改善未来SLE临床试验的设计和结果至关重要。要点 • 选择最佳主要终点指标对SLE临床试验至关重要。 • SLE治疗反应评估中的挑战包括患者异质性和疾病活动评估不一致。 • BICLA和SRI通常用作主要终点指标，但存在显著差异。 • 迫切需要更好的工具来评估SLE临床试验中的疾病活动和反应。
