A Randomized, Controlled Double-Blind Study Comparing the Efficacy and Safety of Dose-Ranging Voclosporin With Placebo in Achieving Remission in Patients With Active Lupus Nephritis

Kidney Int. 2019 Jan;95(1):219-231. doi: 10.1016/j.kint.2018.08.025. Epub 2018 Nov 9.

Abstract

Calcineurin inhibitors added to standard-of-care induction therapy for lupus nephritis (LN) may increase complete renal remission (CRR) rates. The AURA-LV study tested the novel calcineurin inhibitor voclosporin for efficacy and safety in active LN. AURA-LV was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial of two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) versus placebo in combination with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids for induction of remission in LN. The primary endpoint was CRR at 24 weeks; the secondary endpoint was CRR at 48 weeks. Two hundred sixty-five subjects from 79 centers in 20 countries were recruited and randomized to treatment for 48 weeks. CRR at week 24 was achieved by 29 (32.6%) subjects in the low-dose voclosporin group, 24 (27.3%) subjects in the high-dose voclosporin group, and 17 (19.3%) subjects in the placebo group (OR=2.03 for low-dose voclosporin versus placebo). The significantly greater CRR rate in the low-dose voclosporin group persisted at 48 weeks, and CRRs were also significantly more common in the high-dose voclosporin group compared to placebo at 48 weeks. There were more serious adverse events in both voclosporin groups, and more deaths in the low-dose group compared to placebo and high-dose voclosporin groups (11.2%, 1.1%, and 2.3%, respectively). These results suggest that the addition of low-dose voclosporin to mycophenolate mofetil and corticosteroids for induction therapy of active LN results in a superior renal response compared to mycophenolate mofetil and corticosteroids alone, but higher rates of adverse events including death were observed.

Keywords: calcineurin inhibitors; glomerulonephritis; kidney biopsy; proteinuria; systemic lupus erythematosus.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcineurin Inhibitors / administration & dosage*
  • Calcineurin Inhibitors / adverse effects
  • Cyclosporine / administration & dosage*
  • Cyclosporine / adverse effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / methods
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / adverse effects
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / mortality
  • Male
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / adverse effects
  • Remission Induction / methods
  • Treatment Outcome
  • Young Adult

Substances

  • Calcineurin Inhibitors
  • Glucocorticoids
  • Immunosuppressive Agents
  • voclosporin
  • Cyclosporine
  • Mycophenolic Acid