Rapid Reduction in Proteinuria With the Initiation of Voclosporin in Lupus Nephritis: A Single-Center Experience.

Background and purpose Lupus nephritis (LN) is a severe, life-threatening complication of systemic lupus erythematosus (SLE). Reduction in proteinuria is strongly associated with long‑term renal outcomes and is a key endpoint in LN clinical trials. Early initiation of immunosuppressive therapy improves renal recovery, and a rapid decline in proteinuria correlates with achieving remission at 12 months. Voclosporin may cause a mild, early decline in estimated glomerular filtration rate (eGFR) due to hemodynamic effects, which typically stabilizes with continued therapy. This study evaluated the effect of voclosporin on early (≤12‑week) proteinuria reduction and its tolerability when used in combination with standard immunosuppressive therapy in patients with biopsy‑proven LN.  Methods We conducted a retrospective cohort study using the institutional review board-approved Epic Lupus Database at Johns Hopkins Bayview Medical Center, Baltimore, MD, USA. Patients were included if they had biopsy‑confirmed LN and received voclosporin. Demographics, clinical characteristics, and immunosuppressive regimens were abstracted from electronic medical records. Relative changes in urine protein creatinine ratio (UPCR) from baseline to four, eight, and 12 weeks were calculated with corresponding 95% confidence intervals (CIs). Results Twenty‑five patients with biopsy‑proven LN were treated with voclosporin; all received concurrent hydroxychloroquine and tolerated voclosporin without discontinuation. Most patients were treated with mycophenolate or mycophenolic acid (92%) and corticosteroids (96%; median prednisone‑equivalent dose 15 mg/day). Relative reductions in UPCR from baseline were observed at four weeks (-0.27; 95% CI, -0.49 to -0.05), eight weeks (-0.51; 95% CI, -0.65 to -0.37), and 12 weeks (-0.57; 95% CI, -0.71 to -0.43). No statistically significant change in eGFR was observed over the 12‑week treatment period. Conclusion Initiation of voclosporin in combination with standard immunosuppressive therapy in biopsy‑proven LN was associated with early improvement in renal activity, as reflected by significant reductions in UPCR beginning at four weeks. To our knowledge, this represents the largest case series to date describing early real‑world outcomes with voclosporin in LN. Given that persistent proteinuria may indicate ongoing renal inflammation and/or chronic damage, these findings support consideration of voclosporin as a first‑line therapeutic option for active LN.