Utility of leflunomide in the treatment of complex cytomegalovirus syndromes

Robin K. Avery, Sherif B. Mossad, Emilio Poggio, Michelle Lard, Marie Budev, Brian Bolwell, W. James Waldman, William Braun, Steven D. Mawhorter, Richard Fatica, Venkatesh Krishnamurthi, James B. Young, Rabin Shrestha, Brian Stephany, Nell Lurain, Belinda Yen-Lieberman

Research output: Contribution to journalArticle

Abstract

Background. Cytomegalovirus (CMV) viremia that is resistant or refractory to the standard antiviral therapy still constitutes a major threat to high-risk transplant recipients. In addition, multiple CMV recurrences may lead to neutropenia because of repeated courses of therapy with ganciclovir derivatives. Leflunomide, a drug for rheumatoid arthritis, has been reported to have anti-CMV activity. This study reports on its use in 17 transplant recipients with complex CMV syndromes who had failed or were intolerant to other therapies. Methods. Single-center, retrospective study. Clinical data were extracted from the electronic medical record. CMV DNA viral loads were performed by quantitative hybrid capture assay. Results. Leflunomide was initiated after a median of three episodes of CMV viremia, with a mean peak viral load of 245,826 copies/mL. Initial clearance of CMV viremia was observed in 14 of 17 patients (82%), and 9 of 17 (53%) patients achieved a long-term suppression of CMV recurrences. Higher peak viral load and higher viral load at the start of leflunomide therapy were associated with failure to suppress viremia. The duration of leflunomide therapy ranged from 1 to 24 months (median 3.5 months, interquartile range 2.6-7 months), and the mean time to an undetectable CMV-DNA was 1.9 months. Adverse effects included diarrhea (35%), anemia (18%), and increased liver function tests (12%). Conclusions. Leflunomide, alone or in combination, has potential utility in treatment of complex CMV syndromes and in long-term suppression of viremia. The optimal duration of therapy and the balance of risks and benefits are not yet known.

Original languageEnglish (US)
Pages (from-to)419-426
Number of pages8
JournalTransplantation
Volume90
Issue number4
DOIs
StatePublished - Aug 27 2010
Externally publishedYes

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Keywords

  • CMV
  • antiviral therapy
  • ganciclovir resistance
  • leflunomide

ASJC Scopus subject areas

  • Transplantation

Cite this

Avery, R. K., Mossad, S. B., Poggio, E., Lard, M., Budev, M., Bolwell, B., James Waldman, W., Braun, W., Mawhorter, S. D., Fatica, R., Krishnamurthi, V., Young, J. B., Shrestha, R., Stephany, B., Lurain, N., & Yen-Lieberman, B. (2010). Utility of leflunomide in the treatment of complex cytomegalovirus syndromes. Transplantation, 90(4), 419-426. https://doi.org/10.1097/TP.0b013e3181e94106