Voclosporin: A comprehensive review of its role as a novel calcineurin inhibitor in the management of systemic lupus erythematosus

Medicine (Baltimore). 2025 Jun 20;104(25):e42858. doi: 10.1097/MD.0000000000042858.

Abstract

Systemic lupus erythematosus is an autoimmune disease with diverse clinical manifestations, including lupus nephritis. Calcineurin inhibitors (CNIs) are a treatment option, but traditional CNIs have limitations. Voclosporin, a novel oral CNI, inhibits calcineurin to modulate T-cell activation and stabilize podocytes in lupus nephritis. This review assesses voclosporin's therapeutic potential in treating SLE (lupus nephritis), examining its mechanism of action, clinical efficacy, safety profile, and advantages over other CNIs. A broad search was conducted to identify studies published from 2009 to 2024 on voclosporin and other CNIs in lupus nephritis, using databases such as PUBMED, SCOPUS, Google Scholar and Cochrane Library. MeSH Keywords included "voclosporin," "lupus nephritis," "systemic lupus erythematosus," and "calcineurin inhibitors." Studies were included if they reported relevant clinical outcomes, evaluated voclosporin in lupus nephritis, or provided comparative data on voclosporin versus other CNIs, focusing on randomized controlled trials, systematic reviews, meta-analyses, retrospective studies and cohort studies. Voclosporin demonstrated higher renal response rates at 52 weeks than standard treatment alone (40.8% vs 22.5%). It has stable pharmacokinetics, reducing the need for individualized dose adjustments and frequent monitoring. Safety outcomes show a lower incidence of adverse effects like hypertension and hyperlipidemia compared to traditional CNIs. Voclosporin offers superior efficacy and safety compared to traditional CNIs for managing lupus nephritis, with predictable dosing and a favorable side effect profile. Continued research is needed to optimize voclosporin's use and support personalized medicine approaches.

Keywords: calcineurin inhibitors; lupus nephritis; systemic lupus erythematosus; voclosporin.

Publication types

  • Review

MeSH terms

  • Calcineurin Inhibitors* / pharmacology
  • Calcineurin Inhibitors* / therapeutic use
  • Cyclosporine* / adverse effects
  • Cyclosporine* / pharmacology
  • Cyclosporine* / therapeutic use
  • Humans
  • Immunosuppressive Agents* / pharmacology
  • Immunosuppressive Agents* / therapeutic use
  • Lupus Erythematosus, Systemic* / drug therapy
  • Lupus Nephritis* / drug therapy

Substances

  • Calcineurin Inhibitors
  • Cyclosporine
  • voclosporin
  • Immunosuppressive Agents