Journal Article

Lessons Learnt from the Belimumab Trials in Systemic Lupus Erythematosus

Palazzo, Leonardo, Parodis, Ioannis, Nikolopoulos, Dionysis, Tsoi, Alexander

2025

Overview

Belimumab, a human monoclonal antibody that works against B-cell activating factor (BAFF), has significantly advanced the management of systemic lupus erythematosus (SLE). Beyond the initial Phase III randomised controlled trials (RCTs) that demonstrated efficacy for belimumab as an add-on to non-biological standard therapy (ST) along with a favourable safety profile, more than 50 post hoc analyses of RCT data have provided additional insights into its clinical utility. These analyses have shown uniformly that belimumab increases the likelihood of achieving meaningful reductions in disease activity, sustained low disease activity, and improved health-related quality of life (HRQoL) outcomes, with more pronounced benefits in serologically active SLE. Studies focusing on organ-specific manifestations revealed that belimumab confers benefits across multiple SLE facets, with prominent effects on musculoskeletal and mucocutaneous symptoms. Along the same lines, post hoc analyses of the BLISS-LN trial demonstrated benefit from belimumab regarding multiple renal outcomes, including reduced renal flare rates, improved glomerular filtration rate, and improved histological findings in repeat kidney biopsies. Long-term extension studies and real-world evidence confirm its durable efficacy and safety, with continued reductions in overall disease activity, glucocorticoid use, and healthcare resource utilisation over several years. By exploring different efficacy endpoints, person-centred outcomes, disease trajectories, and characteristics across organ manifestations, this body of post-marketing evidence has not only enhanced our understanding of belimumab use in SLE but also constitutes a comprehensive framework for future clinical trial design and development of novel therapeutic strategies. The present review summarises key findings of post hoc analyses of RCTs and observational studies of belimumab.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Antibodies / Antibodies, Monoclonal, Humanized - therapeutic use / B cell therapies / belimumab / BLISS / Clinical trials / Humans / Immunosuppressive Agents - therapeutic use / Lupus / Lupus Erythematosus, Systemic - drug therapy / outcome measures / Patients / post hoc analysis / Quality of Life / Randomized Controlled Trials as Topic / Regulatory approval / Review / systemic lupus erythematosus / Treatment Outcome