title: Utility of leflunomide in the treatment of complex cytomegalovirus syndromes.
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.
authors.affiliation: Department of Infectious Disease, Medicine Institute, The Cleveland Clinic, Cleveland, OH, USA. averyr@ccf.org
authors.forename: Robin K
authors.initials: RK
authors.lastname: Avery
authors.forename: Sherif B
authors.initials: SB
authors.lastname: Mossad
authors.forename: Emilio
authors.initials: E
authors.lastname: Poggio
authors.forename: Michelle
authors.initials: M
authors.lastname: Lard
authors.forename: Marie
authors.initials: M
authors.lastname: Budev
authors.forename: Brian
authors.initials: B
authors.lastname: Bolwell
authors.forename: W James
authors.initials: WJ
authors.lastname: Waldman
authors.forename: William
authors.initials: W
authors.lastname: Braun
authors.forename: Steven D
authors.initials: SD
authors.lastname: Mawhorter
authors.forename: Richard
authors.initials: R
authors.lastname: Fatica
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnamurthi
authors.forename: James B
authors.initials: JB
authors.lastname: Young
authors.forename: Rabin
authors.initials: R
authors.lastname: Shrestha
authors.forename: Brian
authors.initials: B
authors.lastname: Stephany
authors.forename: Nell
authors.initials: N
authors.lastname: Lurain
authors.forename: Belinda
authors.initials: B
authors.lastname: Yen-Lieberman
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000188:drug therapy*; D015774:Ganciclovir / Q000627:therapeutic use; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007555:Isoxazoles / Q000627:therapeutic use*; D000077339:Leflunomide; D016040:Lung Transplantation; D056687:Off-Label Use; D016377:Organ Transplantation; D012189:Retrospective Studies; D018570:Risk Assessment; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D000077339:Leflunomide; D015774:Ganciclovir