Comparison of Dual-Immunosuppressive Therapy and a Voclosporin-Based, Triple-Immunosuppressive Regimen for Lupus Nephritis: A Propensity Analysis of ALMS and AURORA 1

Background: To understand the safety and efficacy of a voclosporin-based, MMF and glucocorticoid-sparing, triple immunosuppressive regimen as an initial approach to therapy in active lupus nephritis (LN) compared to conventional high-dose MMF and glucocorticoid regimens, we compared and analyzed clinical data in propensity-matched patients from ALMS and AURORA 1. We hypothesized that a voclosporin-based, triple immunotherapy approach would reduce exposure to toxicities associated with glucocorticoids and MMF, resulting in an improved safety profile without compromising efficacy. Methods: Both studies enrolled participants with active LN. In ALMS, MMF was dosed to a target of 3 g/day with oral glucocorticoids initiated at a maximum dose of 60 mg/day and tapered every 2 weeks to 10 mg/day. In AURORA 1, participants received voclosporin 23.7 mg BID in combination with MMF at a target dose 2 g/day and oral glucocorticoids started at 25 mg/day and tapered to 2.5 mg/day by Week 16. Propensity matching generated 2 groups of matched patients based on demographic and disease characteristics. Safety and efficacy outcomes were assessed at 3 and 6 months. Results: Propensity matching identified 96 pairs of participants with similar demographics and baseline disease characteristics. At 3 and 6 months, MMF and glucocorticoid exposure was more than 2-fold higher in ALMS than AURORA 1. Overall, fewer adverse events (AE) were observed in AURORA 1 across the majority of organ systems, including gastrointestinal, skin and subcutaneous tissues, endocrine, and psychiatric disorders, although more patients in AURORA 1 were reported to experience eGFR decrease; most reductions in eGFR were manageable by dose modification. The incidence of serious AEs was similar in both groups at 3 and 6 months. In the first 3 months, significantly more patients in AURORA 1 achieved >25% UPCR reduction from baseline (81.3% AURORA 1, 65.6% ALMS; p=0.011); the proportions of patients achieving UPCR ≤0.5 mg/mg and >50% UPCR reduction from baseline were numerically greater in the voclosporin arm; the differences were not statistically significant. Conclusions: The above findings affirm the KDIGO 2023 recommendation that a voclosporin-based, triple-immunotherapy regimen should be considered as initial therapy in active LN. Funding: Commercial Support - Aurinia Pharmaceuticals Inc.

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