medwireNews: Adding the calcineurin inhibitor voclosporin to background immunosuppressive therapy improves renal response rates among people with lupus nephritis, show phase 3 trial results published in The Lancet.
The AURORA 1 study was conducted at 142 centers across North and Latin America, Europe, South Africa, and Asia, and included patients with a diagnosis of systemic lupus erythematosus and active class III, IV, or V lupus nephritis confirmed by biopsy in the previous 2 years.
Robert Huizinga (Aurinia Pharmaceuticals, Victoria, British Columbia, Canada) and co-investigators report that the complete renal response rate at 1 year was 41% for the 179 participants who were randomly assigned to receive add-on oral voclosporin 23.7 mg twice daily, compared with 23% for the 178 patients given add-on placebo, a significant difference.
The composite endpoint of complete renal response was defined as a urine protein:creatinine ratio (UPCR) of 0.5 or less, estimated glomerular filtration rate (eGFR) of at least 60 mL/min per 1.73m2 or no confirmed eGFR decrease of more than 20% from baseline, no requirement for rescue medication, and no more than 10 mg/day prednisone equivalent for 3 consecutive days or for 7 or more days in weeks 44–52.
“The improved complete renal response rate in this study is realised with far less corticosteroid than traditionally used in the treatment of lupus nephritis,” say Huizinga and team, noting that standard therapies “are associated with considerable toxicity, much of which is due to the use of high-dose steroids during the initial phase of treatment.”
They explain that background therapy in both groups comprised mycophenolate mofetil 1 g twice daily plus intravenous methylprednisolone 0.25–0.5 g/day for 2 days followed by rapidly tapering oral prednisone with a starting dose of 20–25 mg/day.
The AURORA 1 trial also demonstrated a significant reduction in proteinuria, as measured by UPCR, among participants treated with voclosporin versus placebo during the first 6 months of follow-up, and this was maintained at the 1-year follow-up. The median time to 50% reduction in UPCR was significantly shorter in the voclosporin than in the placebo arm, at 29 versus 63 days.
“These results are encouraging as the rapid reduction of proteinuria within the first year of treatment is a crucial outcome associated with preservation of kidney function and improvement of long-term outcomes,” write the investigators.
They say that the safety profile was balanced in the voclosporin and control groups, with adverse events (AEs) occurring in 91% and 89% of patients, respectively, and serious AEs reported in 21% of individuals in both groups. The most frequent AEs in both arms were infections and infestations, affecting 65% of voclosporin-treated patients and 57% of those given placebo.
Taken together with previous phase 2 trial results, the AURORA 1 findings “represent an important advancement in the treatment of patients with active lupus nephritis,” conclude Huizinga et al.
Writing in an accompanying comment, Chi Chiu Mok (Tuen Mun Hospital, Hong Kong Special Administrative Region, China) says that although AURORA 1 is one of the largest lupus nephritis trials conducted to date, the study had a number of limitations, including lack of information on extrarenal flares and a long time interval between renal biopsy and study entry.
He recommends that “[c]ost-effectiveness analyses are needed to determine the value of combining voclosporin with standard regimens as induction or rescue therapy for lupus nephritis.”
Voclosporin was approved as an add-on treatment for lupus nephritis by the US FDA in early 2021.
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