CO:11:3 | Belimumab for lupus nephritis patients with poor kidney function: a post-hoc analysis of the bliss-ln trial

Giacomo Emmi^1|2, Ersilia Lucenteforte³, Giorgio Limoncella³, Emanuele Chiara^1|2, Marta Calatroni^4|5, Gabriella Moroni^4|5 | ¹Clinical Medicine and Rheumatology Unit, Cattinara University Hospital, Trieste, Italy; ²Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy; ³Department of Statistics, Informatics and Applications Giuseppe Parenti, University of Florence, Florence, Italy; ⁴Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; ⁵Nephrology and Dialysis Division, IRCCS Humanitas Research Hospital, Milan, Italy

Aim. Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease that presents significant challenges in terms of morbidity and mortality, particularly due to the development of Lupus Nephritis (LN). Impaired renal function at the onset of LN is a crucial predictor of poor long-term outcomes, making timely and effective intervention imperative. The BLISS-LN trial demonstrated that belimumab, when combined with mycophenolate mofetil (MMF) or cyclophosphamide, improves renal response rates among SLE patients. However, patients with compromised renal function, defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m², were specifically excluded from this trial. This post-hoc analysis of the BLISS-LN trail aims at evaluating the efficacy of belimumab in patients with LN who present with a moderate-to-severe renal failure.

Methods. We conducted a post-hoc analysis of patients from the BLISS-LN trial who had an eGFR <60 ml/min/1.73 m² at baseline. The primary outcome measures included the Primary Efficacy Renal Response Rate (PERR) and Complete Renal Response Rate (CRR) assessed at weeks 52 and 104 as defined in the BLISS-LN trial. Secondary outcomes focused on improvements in eGFR, and time to renal-related events. Statistical analyses were performed based on an intention-to-treat approach, and Kaplan-Meier curves were utilized for evaluating time-to-event outcomes, providing a comprehensive understanding of the treatment's impact over time.

Results. A total of 74 patients were included in this analysis, with 41 receiving belimumab and 33 receiving placebo. The baseline characteristics were comparable between treatment groups, ensuring a fair evaluation of outcomes. At week 52, the PERR was found to be 19.5% in the belimumab group compared to 33.3% in the placebo group, while the CRR was 12.2% versus 9.1%, respectively. By week 104, PERR was achieved in 29.3% of patients receiving belimumab compared to 33.3% in the placebo group. Notably, patients treated with belimumab exhibited higher rates of eGFR recovery across all thresholds (10%, 20%, 30%, and 50%) at week 104 compared to those on placebo (Figure 1). However, the incidence of renal-related events or death did not significantly differ between the two groups.

Conclusions. While PERR, CRR, and incidence of renal-related events or death did not demonstrate significant differences between the belimumab and the placebo groups, patients with LN treated with belimumab exhibited meaningful improvements in eGFR. Such recovery is essential for enhancing kidney function and preventing long-term complications, such as the risk of chronic kidney disease. These findings highlight the potential of belimumab to provide additional benefits for LN patients with compromised kidney function, underscoring the need for further investigation into its therapeutic implications in this high-risk population.