Safety, tolerability, and efficacy of everolimus in De Novo liver transplant recipients: 12- and 36-month results

Gary Levy, Heinz Schmidli, Jeffrey Punch, Elizabeth Tuttle-Newhall, David Mayer, Peter Neuhaus, Didier Samuel, Bjorn Nashan, Juergen Klempnauer, Alan Langnas, Yvon Calmus, Xavier Rogiers, Michael Abecassis, Richard Freeman, Maarten Sloof, John Roberts, Lutz Fischer

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104 Scopus citations

Abstract

Everolimus is a macrolide immunosuppressive agent with known consistent absorption. In this double-blind study, we examined the safety and tolerability of everolimus vs. placebo in de novo liver transplant recipients. One hundred and nineteen liver allograft recipients were randomized to 1 of 4 groups: everolimus 0.5 mg bid, everolimus 1.0 mg bid, everolimus 2 mg bid, or placebo. Patients received oral cyclosporine to achieve a target trough level of 150-400 ng/mL in combination with prednisone. Primary and secondary endpoints of safety, tolerability, and efficacy were determined at 12 months, and patients were followed through 36 months. There was a trend toward fewer treated acute rejections in the everolimus group than in the placebo group: everolimus 0.5 mg: 39.3%; everolimus 1.0 mg: 30.0%; everolimus 2 mg: 29.0%; placebo: 40.0% (P = not significant). Adverse events were higher in everolimus-treated patients especially at the 4-mg/day dose, but there was no difference in the incidence of thrombocytopenia or leukopenia between all groups and renal function as determined by serum creatinine, and creatinine clearance remained stable to 36 months in everolimus-treated patients. Mean cholesterol and triglycerides increased from baseline in all treatment groups, and maximum levels were seen at 6 months. In conclusion, this study demonstrates that everolimus in combination with oral cyclosporine had an acceptable safety and tolerability profile, paving the way for additional studies in this transplant indication.

Original languageEnglish (US)
Pages (from-to)1640-1648
Number of pages9
JournalLiver Transplantation
Volume12
Issue number11
DOIs
StatePublished - Nov 1 2006

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ASJC Scopus subject areas

  • Surgery
  • Hepatology
  • Transplantation

Cite this

Levy, G., Schmidli, H., Punch, J., Tuttle-Newhall, E., Mayer, D., Neuhaus, P., Samuel, D., Nashan, B., Klempnauer, J., Langnas, A., Calmus, Y., Rogiers, X., Abecassis, M., Freeman, R., Sloof, M., Roberts, J., & Fischer, L. (2006). Safety, tolerability, and efficacy of everolimus in De Novo liver transplant recipients: 12- and 36-month results. Liver Transplantation, 12(11), 1640-1648. https://doi.org/10.1002/lt.20707