Can disease activity and treatment responses be captured by a core set of domains in SLE clinical trials? An analysis of phase III belimumab trial data.

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: 89.5% concordance rate (1278/1426 patients)

• Primary Outcome: Concordance between core set and full BILAG assessment for treatment response classification

• Nnt Or Sensitivity: 93.5% sensitivity for capturing baseline disease activity with core set

• Confidence Interval: Not reported

Clinical Application

High feasibility - reduces assessment burden from 86 to 30 items while maintaining clinical validity Relevant to Australian rheumatologists conducting SLE research and clinical trials. Aligns with RACGP chronic disease management principles and could inform PBS listing requirements for new SLE therapies Patients with systemic lupus erythematosus enrolled in clinical trials, particularly those with active disease across multiple organ systems

Abstract

OBJECTIVE: Outcome measures used in SLE randomised controlled trials (RCTs) have impeded trial success and drug approval. In an ongoing global project to develop a novel outcome measure for SLE RCTs, a 'core set' of domains with which to determine treatment response was chosen via consensus. We investigated the impact of restricting disease activity assessment to this core set on responder classification in RCTs. METHODS: Using pooled baseline and week 52 data from two phase III SLE RCTs (Belimumab in Subjects with Systemic Lupus Erythematosus (BLISS)-52, NCT00424476; BLISS-76, NCT00410384), we divided items from the British Isles Lupus Assessment Group (BILAG) disease activity index into core and non-core sets. The core set included 30 of 86 BILAG items across five domains: mucocutaneous (rash, alopecia, mucosal ulcers), haematological (thrombocytopenia, haemolytic anaemia), arthritis, serositis and nephritis. We analysed baseline disease activity and treatment response at week 52. RESULTS: We analysed 1526 patients. At baseline, the core set captured the majority of disease activity captured using the full BILAG (1426/1526 (93.5%) of patients). Cutaneous vasculitis, non-haemolytic anaemia, leucopenia, dyspnoea and fatigue were the most common non-core set manifestations present. At week 52, about 1278/1426 (89.5%) patients demonstrated concordant treatment responses measured with the core set only versus all BILAG items. Discordance was again driven by cutaneous vasculitis, non-haemolytic anaemia, leucopenia and fatigue. CONCLUSIONS: Limiting the classification of treatment response to a core set of domains has the potential to simplify SLE RCT endpoints without a significant negative impact on patient inclusion or responder classification.

References

1. 1.Lin, A., Kandane-Rathnayake, R., Morand, E. F., & Connelly, K. (2026). Can disease activity and treatment responses be captured by a core set of domains in SLE clinical trials? An analysis of phase III belimumab trial data. Lupus Science & Medicine. https://doi.org/10.1136/lupus-2025-001928