The importance of developing reproducible primary endpoints for clinical trials in systemic lupus erythematosus

Objective: 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.

Method: 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.

Results: 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.

Conclusions: 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.