Voclosporin Improves Renal Outcomes in Patients With Proliferative Lupus Nephritis with High Proteinuria

In post hoc analyses of AURORA 1, a randomized, double-blind, placebo-controlled, multicenter trial, the addition of voclosporin to mycophenolate mofetil (MMF) and low-dose glucocorticoids improved renal outcomes in patients with proliferative lupus nephritis (LN) and high levels of proteinuria. Participants treated with voclosporin showed higher rates of complete renal response and a faster reduction in proteinuria compared to those receiving a placebo.

The standard treatment regimen of MMF and low-dose glucocorticoids for LN has shown limited success in achieving complete renal remission, especially in patients with high levels of proteinuria. Voclosporin has demonstrated benefits in improving renal outcomes in LN, but its efficacy in patients with proliferative LN and high proteinuria had not been fully evaluated. This study aimed to examine the efficacy and safety of adding voclosporin to MMF and low-dose glucocorticoids in this patient subgroup.

The study enrolled adults with class III or IV (±class V) LN and a baseline urine protein-creatinine ratio (UPCR) of greater than or equal to 3 g/g (N = 148). Participants were randomly assigned to receive either voclosporin (23.7 mg twice daily) or placebo for 12 months, in addition to MMF and low-dose glucocorticoids. Efficacy outcomes included complete renal response, partial renal response, and the trajectory of proteinuria over time. Safety was also evaluated, focusing on adverse events and kidney function, specifically estimated glomerular filtration rate (eGFR).

The results showed that 34% of participants who received voclosporin achieved a complete renal response at 12 months, compared to 11% in the placebo arm (odds ratio [OR] = 4.43; 95% CI, 1.78 to > 9.99; P =  .001). For partial renal response, 65% of voclosporin-treated participants achieved ≥50% reduction in UPCR, compared with 51% in the control group, though the difference was not statistically significant (OR = 1.60; 95% CI, 0.8 to 3.20; P = .18). More voclosporin-treated patients achieved a UPCR less than or equal to 0.5 g/g (51% vs 26%), and this endpoint was reached earlier than the control-treated group (hazard ratio = 2.07; 95% CI, 1.19 to 3.60; P = .01). Both treatment groups showed stable and normal eGFR values, and adverse event rates were similar between groups.

The study's limitations include its post hoc design, and its relatively small sample size. The trial’s 12-month duration also may not allow for full assessment of voclosporin’s long-term safety and efficacy.

 “The addition of voclosporin to MMF and low-dose glucocorticoids resulted in a significantly higher proportion of participants with proliferative lupus nephritis achieving complete and partial renal responses as well as earlier reductions in proteinuria, with no evidence of worsening kidney function,” the study authors concluded.

Reference

Menn-Josephy H, Hodge LS, Birardi V, Leher H. Efficacy of voclosporin in proliferative lupus Nephritis with High Levels of Proteinuria. Clin J Am Soc Nephrol. 2024;19(3):309-318. doi:10.2215/CJN.0000000000000297