1544: Voclosporin in Lupus Nephritis: Meta-Analysis of 6-Month and 1-Year Efficacy with 1-Year Safety Outcomes

Background/Purpose: Lupus nephritis (LN), is the most sever organ manifestation of systemic lupus erythematosus (SLE) and it contributes significantly to morbidity and mortality. . Standard therapies—high-dose corticosteroids combined with mycophenolate mofetil or cyclophosphamide—achieve complete renal remission in a limited subset of patients and carry substantial toxicity. Calcineurin inhibitors (CNIs) target immune dysregulation and podocyte injury. Voclosporin, a novel CNI, inhibits T-cell activation and reduces proteinuria, offering potential therapeutic benefit in LN.

Methods: A systematic search of PubMed, Embase, and Cochrane databases was conducted for English-language studies evaluating voclosporin in LN and reporting relevant efficacy or safety outcomes. Two randomized controlled trials met inclusion criteria. Data were pooled using inverse variance weighting with a random-effects model in R Studio. Forest plots were used to illustrate pooled effect estimates, and heterogeneity was assessed.

Results: A total of 533 patients from two studies were included. Voclosporin significantly increased complete renal response (CRR) at 6 months (RR 1.67; 95% CI: 1.24–2.25; p=0.0008) and 1 year (RR 1.91; 95% CI: 1.48–2.48; p< 0.0001) compared to placebo. Rates of overall adverse events (RR 1.04; 95% CI: 0.98–1.10; p=0.16), serious adverse events (RR 1.26; 95% CI: 0.71–2.25; p=0.43), and infections (RR 1.15; 95% CI: 0.98–1.36; p=0.096) were similar between groups. However, voclosporin was associated with significantly higher gastrointestinal (RR 1.37; 95% CI: 1.06–1.76; p=0.016) and neurological adverse events (RR 1.79; 95% CI: 1.18–2.72; p=0.006) at 1 year.

Conclusion: Voclosporin significantly improves CRR at 6 months and 1 year in patients with LN, with an overall safety profile comparable to placebo. However, gastrointestinal and neurological adverse events were more common. Further studies are needed to assess long-term outcomes, define steroid-sparing protocols, optimize dosing, and evaluate efficacy across diverse populations to determine voclosporin’s definitive role in LN treatment.