POS-390 ELECTROLYTE PROFILES OF LUPUS NEPHRITIS PATIENTS TREATED WITH THE NOVEL CALCINEURIN INHIBITOR VOCLOSPORIN

Abstract

Electrolyte imbalances, which can be modulated within the kidney, have been previously reported with calcineurin inhibitor (CNI) utilization in solid organ transplant.1,2Dietary supplementation of electrolytes may correct serum electrolyte imbalances; therefore, it can be useful to evaluate urinary excretion over time to detect changes in electrolytes due to diet or to confirm clinical findings in serum. Voclosporin is a novel CNI approved in the US for the treatment of adult patients with active lupus nephritis in combination with background immunosuppressive therapy. Data from the pivotal Phase 3 AURORA 1 study showed that the addition of voclosporin to mycophenolate mofetil (MMF) and low-dose steroids results in higher complete renal response rates at one year (40.8% vs 22.5%; OR 2.65; p<0.0001) in patients with lupus nephritis. AURORA 1 was a double-blind, randomized controlled trial designed to evaluate oral voclosporin (23.7 mg twice daily) compared to placebo in patients with active lupus nephritis, with all patients receiving MMF (target dose 1 g twice daily) and low-dose oral steroids (rapidly tapered to 2.5 mg daily at week 16). Serum electrolyte imbalances including hypomagnesemia are common adverse events associated with CNIs. In contrast to these reports, mean serum electrolyte concentrations of patients treated with voclosporin were within normal ranges in AURORA 1. As serum electrolytes concentrations can be impacted by dietary supplementation, we evaluated urinary excretion rates to assess if inadvertent dietary supplementation during the study had impacted the findings in serum. Twenty-four-hour urine samples from 60 patients in each treatment arm were selected including patients that responded to treatment at one year with at least 50% reduction in urine protein creatinine ratio (UPCR) from baseline (treatment responders), those who had not (non-responders), and patients who had at least 30% reduction from baseline in estimated glomerular filtration rate (eGFR) during the study. Mean change from baseline to one year in magnesium, potassium and sodium are presented as 24-hour urinary electrolyte excretion rates. Mean changes from baseline in urinary electrolyte excretion were small for magnesium (≤13.4 mg/24 hours) and potassium (≤6.4 mmol/24 hours) with no significant differences between treatment arms for any of the subgroups. Sodium excretion decreased from baseline in all subgroups (≤30.5 mmol/24 hours) except for responders in the control arm (increase of 14.0 mmol/24 hours) at one year (Table 1). Patients with lupus nephritis in AURORA 1 treated with voclosporin in combination with MMF and low-dose steroids achieved significantly higher complete renal response rates compared to patients treated with only MMF and low-dose steroids. At the doses studied, changes from baseline in urinary electrolyte excretion of magnesium, potassium, and sodium were not clinically meaningful in either treatment arm regardless of response to treatment. These results confirmed dietary supplementation did not impact the findings in serum concentrations. Together with the reported normal electrolyte concentrations in serum, this study confirms voclosporin has no meaningful impact on mean concentrations of electrolytes. This analysis further supports the safety and efficacy of voclosporin for the treatment of patients with lupus nephritis.