Case series of the combination of voclosporin and belimumab treatment of lupus nephritis

Background: Lupus nephritis (LN) remains challenging with high treatment failure and relapse rates. Current therapies often fail to achieve sustained renal remission. Objective: To evaluate the efficacy and safety of combination voclosporin and belimumab therapy in patients with biopsy-confirmed lupus nephritis. Methods: Retrospective case series of 16 female patients (median age 36) with kidney biopsy-proven lupus nephritis treated with voclosporin (15.8-23.7 mg BID) plus belimumab (200 mg SC weekly/IV) between 2012 and 2025 in routine clinical practice. Baseline was defined as the laboratory value closest to the first kidney biopsy. Longitudinal data for urine protein-to-creatinine ratio (UPCR), serum creatinine, C3/C4 complement, and anti-dsDNA antibodies were analyzed using the Wilcoxon signed-rank test. Results: Initiation of voclosporin and belimumab was associated with a marked reduction in proteinuria, with median UPCR declining from 2.175 g/g to 0.082 g/g and remaining low at final follow-up (0.131 g/g; all p ≤ 0.0005). Serologic markers improved concurrently, with increases in complement levels (C3 65.0 to 109.5, C4 6.5 to 20.5) and a decline in median anti-dsDNA (51.5 to 12.0). 62.5% of patients tapered corticosteroids to ≤5 mg/day or discontinued them, while serum creatinine increased modestly from 0.77 to 0.89 mg/dL. Conclusions: The combination of voclosporin and belimumab is highly effective in inducing rapid and sustained renal remission and facilitating significant reduction in corticosteroid dose in patients with lupus nephritis. Clinical Implications: This case series provides real-world evidence supporting the use of a combination of voclosporin and belimumab as an effective, well-tolerated treatment option for lupus nephritis, offering hope for improved long-term renal outcomes in this challenging patient population