Effects of the Intensity of Immunosuppressive Therapy on Outcome of Treatment for CMV Disease in Organ Transplant Recipients

Authors

  • A. Åsberg,

    Corresponding author
    1. Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway
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  • A. G. Jardine,

    1. Department of Medicine, University of Glasgow, Glasgow, UK
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  • A. A. Bignamini,

    1. School of Specialisation in Hospital Pharmacy, University of Milan, Milan, Italy
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  • H. Rollag,

    1. Institute of Microbiology, University of Oslo and Rikshospitalet, Oslo, Norway
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  • M. D. Pescovitz,

    1. Departments of Surgery and Microbiology/Immunology, Indiana University, Indianapolis, IN
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  • C. C. Gahlemann,

    1. F. Hoffmann—La Roche Ltd., Basel, Switzerland
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  • A. Humar,

    1. Department of Medicine, University of Alberta, Edmonton, Canada
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  • A. Hartmann,

    1. Medical Department, University of Oslo and Rikshospitalet, Oslo, Norway
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  • on behalf of the VICTOR Study Group

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    • North America: Sandra Cockfield. Latin America: Anabela Armino, Luis F. A. Carnargo, Carmen Garcia, Carlos Henriquez, Marilda Mazzali, Elias David Neto, Irene L. Noronha, Jose Osmar Medina Pestana, Rfael Reyes. Asia, Pacific Islands and Australia: Allan Glanville, Ian Dittmer, George T. John, Vijay Kher, R. K. Sharma, C. M. Thiagarjan. Europe and Middle East: Jose Maria Aguado, Emel Akoglu, Hofman Blazenka, Felix Burkhalter, Magdalena Durlik, Antonio Franco Esteve, Marciej Glyda, Abdul Hammad, Rajko Hrvacevic, Madis Ilmoja, Marian Klinger, Dirk Kuypers, Phil Mason, Miguel Montejo, Mai Ots, Patrik Peters, Rafails Rozentals, Boleslaw Rutkowski, Sabine Schmaldienst, Juerg Steiger, M. Tuncer, Hüseyn Töz, Zbigniew Wlodarczyk, Michael Zakliczynski.


Corresponding author: Anders Åsberg, anders.asberg@farmasi.uio.no

Abstract

An effective host immune response, critical for successful control of Cytomegalovirus (CMV) disease in solid organ transplant recipients, is affected by intensity and type of immunosuppressive therapy. We used information prospectively captured in the VICTOR-trial to investigate the impact of immunosuppressive therapy on short- and long-term outcomes of CMV treatment in organ transplant recipients. Dual, as compared to triple, immunosuppressive therapy ([odds ratios] OR of 2.55; 95% CI: 1.51–4.60; p = 0.002), lower blood concentrations of calcineurin inhibitors (OR of 5.53; CI: 1.04–29.35; p = 0.045), and longer time since transplantation (OR of 1.70; CI: 1.01–2.87; p = 0.047) all showed better early (Day 21) CMV DNAemia eradication. We observed no effect of the intensity of the immunosuppressive therapy on overall rates of viral eradication or recurrence. The type of calcineurin inhibitor (tacrolimus/cyclosporine) or use of mycophenolate did not affect treatment efficacy, although both tacrolimus and mycophenolate treated patients showed a lower rate of virological recurrence OR 0.51 (95% CI: 0.26–0.98; p = 0.044) and OR 0.45 (95% CI: 0.22–0.93; p = 0.031), respectively. Lower total intensity of immunosuppressive therapy was associated with more effective early, but not overall, CMV DNAemia eradication by valganciclovir/ganciclovir therapy. Both mycophenolate and tacrolimus (rather than cyclosporine) therapy seem to be associated with reduced risk of recurrence.

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