Leflunomide as adjunct therapy for BK viremia management in pediatric kidney transplant recipients

Author:

Aldieri Alexandra1ORCID,Chandran Mary2,Matossian Debora3ORCID,Hariprasad Aparna3,Magella Bliss4,Lazear Danielle5,Blanchette Eliza6,Benz Eric6ORCID,Bock Margret6ORCID

Affiliation:

1. Pharmacy Phoenix Children's Hospital Pheonix Arizona USA

2. Pharmacy University of North Carolina Health Chapel Hill North Carolina USA

3. Pediatrics, Nephrology, Ann & Robert H. Lurie Children's Hospital of Chicago Northwestern University Chicago Illinois USA

4. Pediatrics, Endocrinology, Cincinnati Children's Hospital Medical Center University of Cincinnati Cincinnati Ohio USA

5. Pharmacy Horizon Therapeutics Thousand Oaks California USA

6. Pediatrics, Nephrology, Children's Hospital Colorado University of Colorado School of Medicine Aurora Colorado USA

Abstract

AbstractBackgroundBK viremia after kidney transplantation (KT) poses significant risk for BK virus‐associated nephropathy and impacts graft survival. Conventional treatment involves reduction of immunosuppression, which in turn may increase risk for rejection. To address this dilemma, use of anti‐viral therapy with immunosuppressive properties such as leflunomide is an attractive option.MethodsWe performed a multi‐center, retrospective chart review to report tolerability and effectiveness of leflunomide use for the eradication of BK viremia and prevention of BK virus‐associated nephropathy in pediatric KT recipients.ResultsSeventy patients prescribed leflunomide were included and were followed up from initiation until 1 year following leflunomide completion. BK viremia was eradicated in 64 (91.4%) patients including 8 of 11 with nephropathy (BKVN) on initial biopsy. Reduced anti‐proliferative medication (AP) dosing was not associated with increase in biopsy proven rejection (BPAR). However, complete discontinuation of AP during leflunomide therapy was associated with increase in BPAR in uni‐ and multivariate logistic regression, as was targeted reduction in calcineurin inhibitor (CNI) trough goals. One graft was lost to BKVN. There was no significant association found between time to BK eradication and leflunomide trough concentration, mycophenolate dose reduction, or steroid use (univariate logistic regression). Few leflunomide adverse drug reactions (ADR) were reported (most commonly: gastrointestinal, hematologic).ConclusionLeflunomide is a promising adjunctive treatment to immunosuppression reduction for BK virus eradication with minimal ADR. AP reduction, not discontinuation, and judicious reduction in CNI trough goals with close monitoring, is a promising strategy for treatment of BK viremia with concomitant use of leflunomide therapy.

Publisher

Wiley

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