Everolimus versus azathioprine in maintenance lung transplant recipients: An international, randomized, double-blind clinical trial

G. I. Snell, V. G. Valentine, P. Vitulo, A. R. Glanville, D. C. McGiffin, J. E. Loyd, A. Roman, R. Aris, A. Sole, A. Hmissi, U. Pirron

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Everolimus is a proliferation signal inhibitor with immunosuppressive activity that may reduce the rate of progression of chronic rejection, bronchiolitis obliterans syndrome (BOS), after lung transplantation. In a randomized, double-blind clinical trial, 213 BOS-free maintenance patients received everolimus (3 mg/day) or azathioprine (AZA, 1-3 mg/kg/day) in combination with cyclosporine and corticosteroids. The prospectively defined primary endpoint was the incidence of efficacy failure (decline in FEV 1 >15%[ΔFEV1 >15%], graft loss, death or loss to follow-up) at 12 months. Incidence of efficacy failure at 12 months was significantly lower in the everolimus group than AZA (21.8% vs. 33.9%; p = 0.046); at 24 months, rates of efficacy failure became similar between the groups. At 12 months, the everolimus group had significantly reduced incidences of ΔFEV1 >15%, ΔFEV1 >15% with BOS, and acute rejection. At 24 months, only incidence of acute rejection remained significantly less in the everolimus group. Treatment discontinuations (particularly due to adverse events), serious adverse events and high serum creatinine values were more common with everolimus. For the first time, a drug has demonstrated significant slowing of loss in lung function, suggesting that patients kept on prolonged maintenance treatment with everolimus may benefit from replacing AZA with everolimus 3 months after lung transplantation.

Original languageEnglish (US)
Pages (from-to)169-177
Number of pages9
JournalAmerican Journal of Transplantation
Volume6
Issue number1
DOIs
StatePublished - Jan 1 2006

Keywords

  • Bronchiolitis obliterans syndrome
  • Everolimus
  • Lung transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Snell, G. I., Valentine, V. G., Vitulo, P., Glanville, A. R., McGiffin, D. C., Loyd, J. E., Roman, A., Aris, R., Sole, A., Hmissi, A., & Pirron, U. (2006). Everolimus versus azathioprine in maintenance lung transplant recipients: An international, randomized, double-blind clinical trial. American Journal of Transplantation, 6(1), 169-177. https://doi.org/10.1111/j.1600-6143.2005.01134.x