Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: a propensity analysis of the AURA-LV and AURORA 1 studies and ALMS.

Autor:	Dall'Era M; University of California San Francisco School of Medicine, San Francisco, California, USA., Kalunian K; University of California San Diego Health Sciences, La Jolla, California, USA., Solomons N; Formerly of Aurinia Pharmaceuticals Inc, Edmonton, Alberta, Canada., Truman M; Aurinia Pharmaceuticals Inc, Edmonton, Alberta, Canada., Hodge LS; Aurinia Pharmaceuticals Inc, Edmonton, Alberta, Canada., Yap E; Aurinia Pharmaceuticals Inc, Edmonton, Alberta, Canada eyap@auriniapharma.com., Askanase AD; Columbia University College of Physicians and Surgeons, New York, New York, USA.
Jazyk:	angličtina
Zdroj:	Lupus science & medicine [Lupus Sci Med] 2024 Nov 09; Vol. 11 (2). Date of Electronic Publication: 2024 Nov 09.
DOI:	10.1136/lupus-2024-001319
Abstrakt:	Introduction: High-dose glucocorticoid (GC)-based dual immunosuppressive treatment regimens are still frequently used in active lupus nephritis (LN) despite their known association with dose-dependent toxicities and incomplete efficacy. We hypothesised that the addition of voclosporin to low-dose GCs and mycophenolate mofetil (MMF) would reduce exposure to the toxicities of high-dose GC-based dual immunosuppressive therapy regimens, resulting in an improved safety profile without compromising efficacy. Methods: Propensity score matching generated two groups of matched participants from the voclosporin arms (in combination with MMF (2 g/day) and low-dose GCs) of the Phase 2 AURA-LV and Phase 3 AURORA 1 studies and the MMF (3 g/day) and intravenous cyclophosphamide (IVC) arms (both in combination with high-dose GCs) of the Aspreva Lupus Management Study (ALMS) induction study. Safety and efficacy outcomes were assessed over 6 months. Results: There were 179 matched participants identified between the AURA-LV/AURORA 1 studies and ALMS. The overall incidence of adverse events (AEs) was higher in IVC- and MMF-treated participants of ALMS; more voclosporin-treated participants reported AEs by preferred term of glomerular filtration rate decreased, hypertension and anaemia. The incidence of serious AEs was similar across treatments. There were four (2.2%) deaths in IVC- and MMF-treated participants of ALMS compared with seven (3.9%) deaths in voclosporin-treated participants. Significantly more voclosporin-treated participants achieved a ≥25% reduction in urine protein creatinine ratio (UPCR) from baseline at 3 months and ≥50% reduction in UPCR from baseline at 6 months. Conclusions: Compared with the high-dose GC-based regimens used in ALMS, voclosporin-based triple immunosuppressive therapy resulted in fewer AEs overall and greater and earlier reductions in proteinuria over the first 6 months of treatment. These data reinforce the feasibility of using low doses of GCs and MMF to treat LN when combined with voclosporin as a third agent. Competing Interests: Competing interests: MD has received grants or contracts from Annexon Biosciences and GSK plc and is a consultant for Annexon Biosciences, AstraZeneca, Aurinia Pharmaceuticals Inc., Biogen, GSK plc and Pfizer. KK has received grants of contracts from UCB and Novartis and is a consultant for BMS, GSK plc, Biogen, AstraZeneca, Equillium, Artiva, Pfizer, Eli Lilly, Gilead and Kyverna. NS is a former employee and shareholder of Aurinia Pharmaceuticals Inc. MT is a consultant for Aurinia Pharmaceuticals Inc. LSH and EY are employees and shareholders of Aurinia Pharmaceuticals Inc. ADA is a consultant for Aurinia Pharmaceuticals Inc., AstraZeneca, GSK plc and Eli Lilly. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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