Journal Article

OP0059 VOCLOSPORIN-BASED, TRIPLE-IMMUNOSUPPRESSIVE REGIMEN VERSUS HIGH-DOSE GLUCOCORTICOID AND MYCOPHENOLATE MOFETIL-BASED THERAPY FOR LUPUS NEPHRITIS: A PROPENSITY ANALYSIS OF THE ALMS, AURA-LV AND AURORA 1 STUDIES

Solomons, N., Kalunian, K. C., Truman, M., Hodge, L., Askanase, A., Dall’era, M., Yap, E.

2024

Overview

Background:Lupus nephritis (LN) is characterized by proteinuria, which is not only a marker of active kidney inflammation, but also a driver of progressive kidney injury. Early reduction in proteinuria following treatment initiation has been shown to be a predictor of long-term kidney survival and overall mortality. The AURA-LV and AURORA 1 clinical trials have shown that voclosporin-based triple therapy with lower-dose MMF, and low-dose glucocorticoids (GCs) led to early and significant reductions in proteinuria with an acceptable safety profile. However, dual-immunosuppressive regimens containing high-dose glucocorticoids (GCs) and higher doses (>2 g/day) of mycophenolate mofetil (MMF) or intravenous cyclophosphamide (IVC) are still frequently used for the management of active LN in the belief that they may be more efficacious and safer.Objectives:To compare the safety and efficacy of a voclosporin-based, triple immunosuppressive regimen to a dual-immunosuppressive regimen for the treatment of active LN, we analyzed outcomes in propensity-matched participants from the ALMS, AURA-LV, and AURORA 1 studies. We hypothesized that a voclosporin-based, triple therapy approach would reduce exposure to the toxicities associated with higher doses of GCs, MMF, and IVC, resulting in an improved safety profile without compromising efficacy.Methods:All three studies enrolled participants with active LN. In AURA-LV and AURORA 1, participants received voclosporin 23.7 mg BID in combination with MMF (target 2 g/day) and oral GCs (25 mg/day tapered to 2.5 mg/day by Week 16). In ALMS, MMF (target 3 g/day) or IVC (0.5 to 1.0 g/m2/month x 6) was added to oral GCs initiated at a maximum dose of 60 mg/day, tapered every 2 weeks to 10 mg/day. Propensity score methodology was used to generate groups of matched participants (ALMS [MMF and IVC] vs. AURA-LV/AURORA 1 [voclosporin]) based on demographic and disease characteristics. Safety and efficacy were assessed at 3 and 6 months.Results:Propensity matching identified 179 participant pairs with similar demographics and baseline disease characteristics. Mean cumulative exposure to GCs was more than 2-fold higher in the IVC and MMF cohorts of ALMS than AURA-LV/AURORA 1 participants over both 3 and 6 months. The overall incidence of adverse events (AEs) was higher in IVC- and MMF-treated participants in ALMS over the 6-month period. More participants in AURA-LV and AURORA 1 reported hypertension and anemia. Due to the known hemodynamic effects of calcineurin inhibition, there was a small decrease in mean eGFR in the AURA-LV/AURORA 1 participants in the first few weeks of treatment after which mean eGFR remained stable; a greater number of events of GFR decreased were reported by AURA-LV/AURORA 1 participants. The incidence of serious AEs was similar across groups. UPCR ≤0.5 mg/mg was achieved by 52% of voclosporin-treated participants compared to 41.1% of IVC- or MMF-treated participants of ALMS; the median time to this endpoint for the voclosporin group was 142 days; a median time was not determinable for ALMS participants as less than 50% achieved the endpoint within the study period (hazard ratio [HR] 1.41; 95% confidence interval [CI] 1.03, 1.94; p=0.0324; Table 1, Figure 1). More voclosporin-treated participants achieved a 50% reduction in UPCR from baseline at any point during the study; this endpoint was met significantly earlier by voclosporin-treated patients as well (29 vs. 84 days; HR 1.88, 95% CI 1.48, 2.39; p<0.0001).Conclusion:Participants treated with voclosporin in combination with low-dose GCs and MMF 2g/day demonstrated an improved safety profile and earlier reductions in proteinuria compared to participants treated with high-dose GCs and MMF up to 3 g/day or IVC. These findings support the recommendation that a voclosporin-based, triple-immunosuppressive regimen should be considered as an initial therapy in patients with active LN.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Anca Askanase Consultant for Aurinia Pharmaceuticals Inc., AstraZeneca, GSK plc., Eli Lilly, Kenneth C. Kalunian: None declared, Maria Dall’Era Consultant for Annexon Biosciences, AstraZeneca, Aurinia Pharmaceuticals Inc., Biogen, GSK plc., and Pfizer, Grant/research support from Annexon Biosciences, GSK plc., Neil Solomons Shareholder of Aurinia Pharmaceuticals Inc., Former employee of Aurinia Pharmaceuticals Inc., Lucy Hodge Shareholder of Aurinia Pharmaceuticals, Inc., Employee of Aurinia Pharmaceuticals, Inc., Matt Truman Consultant for Aurinia Pharmaceuticals, Inc., Ernie Yap Shareholder of Aurinia Pharmaceuticals Inc., Employee of Aurinia Pharmaceuticals Inc.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier B.V,Elsevier Limited
• Subject: Antineutrophil cytoplasmic antibodies / Calcineurin / Clinical Trial / Clinical trials / Cyclophosphamide / Demography / Epidermal growth factor receptors / Glucocorticoids / Immunosuppressive agents / Kidneys / Lupus nephritis / Mycophenolate mofetil / Mycophenolic acid / Patients / Pharmaceuticals / Proteinuria / Safety / Scientific Abstracts / Stockholders / Systemic lupus erythematosus / Yes-associated protein