Everolimus is associated with a reduced incidence of CMV infection in heart transplantation

Abstract

Everolimus is a novel proliferation inhibitor under development for the prevention of rejection in organ transplantation.Purpose: This abstract reports on the 12-month incidence of cytomegalovirus (CMV) infection in the phase 3 heart transplantation study.Methods: Patients (N=634) were randomized to either everolimus 1.5 mg/day (N=209), everolimus 3 mg/day (N=211) or AZA 1–3 mg/kg/day (N=214), with a regimen of cyclosporine (CsA,Neoral), corticosteroids and statins. Laboratory evidence of CMV was determined by antigenemia or PCR. The CMV infection was defined as CMV syndrome (fever for at least 2 days, neutropenia, leukopenia and viral syndrome); or CMV disease (systemic disease with organ involvement); or only laboratory evidence of CMV. CMV prophylaxis was administered in 75% of the patients.Results: Donor/Recipient (D/R) CMV serostatus was evenly distributed across all groups with the high risk group (D+/R-) incidence being 17.2%, 22.7% and 17.3%. Mean duration of CMV prophylaxis was 141, 126 and 110 days in everolimus 1.5 mg, 3 mg and AZA groups respectively (p=ns). The overall incidence of CMV infection was 7.7%, 7.6% and 21.5 % in the everolimus 1.5 mg, 3 mg and AZA groups respectively (p=0.0001). The incidence of CMV syndrome was 1.9% (4 cases), 3.3% (7) and 4.6% (10), and CMV disease was 1.9% (4 cases), 2.3% (5) and 6.5% (14) in everolimus 1.5 mg, 3 mg and AZA groups respectively (p=ns).Conclusions: The incidence of CMV infection was lower in the everolimus groups compared to AZA treated patients and CMV disease was numerically higher in the AZA group. This finding may be of particular significance given the potential role of CMV infection in the development of chronic rejection.