Leflunomide efficacy and pharmacodynamics for the treatment of BK viral infection

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Jill C Krisl1, David J Taber, Nicole Pilch

  • 1Department of Pharmacy Services, Medical University of South Carolina, Charleston, South Carolina, USA. krisl@musc.edu

Clinical Journal of the American Society of Nephrology : CJASN
|March 31, 2012
PubMed
Abstract

Insights

Leflunomide therapy did not improve BK viral clearance in kidney transplant patients. Therapeutic drug monitoring of its metabolite, A77 1726, showed no correlation with BK viral load reduction. Further studies are needed to confirm leflunomide

Area of Science:

  • Nephrology
  • Transplantation Immunology
  • Pharmacology

Background:

  • BK virus infection is a significant threat to kidney transplant graft survival.
  • Current treatment strategies for BK viremia and nephropathy lack consensus.
  • Limited data exist on the therapeutic drug monitoring of leflunomide for BK virus infections.

Purpose of the Study:

  • To investigate the pharmacodynamic relationship between leflunomide metabolite (A77 1726) serum concentrations and BK viral load reduction.
  • To assess the association between leflunomide therapy and BK viral clearance in kidney transplant recipients.

Main Methods:

  • Retrospective, single-center, longitudinal analysis of kidney transplant patients with BK viremia.
  • Correlation of BK viral PCR and A77 1726 serum concentrations with clinical outcomes.
  • Multivariate analysis to identify factors associated with BK viral clearance.

Main Results:

  • No significant correlation was found between A77 1726 concentrations and BK viral load reduction.
  • Leflunomide therapy was not associated with improved BK viral clearance.
  • Mycophenolate mofetil discontinuation and BK viremia (without nephropathy) were associated with clearance.

Conclusions:

  • Pharmacodynamic analysis did not support a link between A77 1726 levels and BK viral reduction.
  • Leflunomide therapy did not demonstrate a significant association with BK viral clearance in this cohort.
  • Randomized controlled trials are necessary to establish the efficacy of leflunomide for BK viremia and nephropathy.

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