Effect of Long-Term Voclosporin Treatment on Renal Histology in Patients With Active Lupus Nephritis With Repeat Renal Biopsies

Abstract

Objective: This study characterized the impact of voclosporin on kidney histology in patients with lupus nephritis (LN) who had protocolized repeat kidney biopsies in the AURORA clinical trials. Methods: Patients were randomized to voclosporin or placebo treatment for up to 3 years; all patients received mycophenolate mofetil and low-dose glucocorticoids. Patients had baseline kidney biopsies within 6 months before study start and repeat biopsies after approximately 18 months of study treatment. The revised National Institutes of Health indices for LN activity and chronicity (CI) were calculated in addition to a semiquantitative assessment of vascular and tubular lesions. Results: Sixteen patients in the voclosporin group and 10 patients in the control group had both baseline and repeat kidney biopsies. Patient clinical characteristics were similar at baseline. In the voclosporin group, most (n = 13) patients had pure class IV lesions (pure class V, n = 1; mixed, n = 2). In the control group, three patients had pure class IV (pure class III, n = 3; pure class V, n = 1; mixed, n = 3). Most of the voclosporin-treated patients had no change in CI (n = 8) or a change no greater than 2 (n = 6); control-treated patients also had no change in CI (n = 3) or a change no greater than 2 (n = 6). No trends in vascular lesions or tubular compartment changes were observed. Conclusion: Outcomes from this small subgroup show that exposure to study treatment was not associated with nephrotoxicity based on histopathologic evaluation after 18 months. These data are reassuring and further contribute to the safety profile of voclosporin for the treatment of adults with active LN.