The effect of anti-thymocyte globulin and everolimus on the kinetics of cytomegalovirus viral load in seropositive kidney transplant recipients without prophylaxis.

BACKGROUND: The use of mTOR inhibitors is associated with lower incidence of CMV infections but its effect on viral load has not been investigated. AIMS, MATERIALS AND METHODS: This post-hoc analysis included data from 273 CMV seropositive kidney transplant recipients randomized to receive anti-thymocyte globulin and everolimus (rAGT/TAC/EVR, n = 81), basiliximab and everolimus (BAS/TAC/EVR, n = 97) or basiliximab and mycophenolate (BAS/TAC/MPS, n = 95). All patients received tacrolimus (TAC) and corticosteroids. Preemptive CMV therapy based on weekly pp65 antigenemia test was used during the first 6 months. Blinded weekly CMV DNAemia was compared among the groups. RESULTS: The proportion of patients with undetectable CMV DNAemia (23.4% vs 56.7% vs 22.1%, P < .001) was higher in the BAS/TAC/EVR. The median number of study visits with positive CMV DNAemia (2.0 vs 0.0 vs 4.6, rATG/EVR vs BAS/MPS, P = .354; BAS/EVR vs BAS/MPS, P < .0001; rATG/EVR vs BAS/EVR, P < .001) were lower in the BAS/TAC/EVR. The proportion of patients with positive CMV DNAemia who were not treat for CMV infection/disease based on pp65 antigenemia was higher in rATG/TAC/EVR group (74.1% vs 36.1% vs 44.2%, P < .001) but mean CMV DNAemia was comparable to BAS/TAC/EVR and lower than BAS/TAC/MPS (8536 ± 15 899 vs 7975 ± 17 935 vs 16 965 ± 37 694 copies/mL, P < .05), respectively. The proportion of patients with CMV DNAemia below 5000 copies/mL was higher in patients receiving EVR (74.1% vs 83.5% vs 50.0%, P = .000), respectively. DISCUSSION AND CONCLUSION: These data suggest that mTOR inhibitors reduce the incidence of CMV infection by limiting CMV viral replication.

Cost-Effectiveness Analysis of Everolimus versus Mycophenolate in Kidney Transplant Recipients Receiving No Pharmacological Prophylaxis for Cytomegalovirus Infection: A Short-Term Pharmacoeconomic Evaluation (12 Months).

BACKGROUND: Modern immunosuppressive regimens, although associated with improved 1-year graft survival, are associated with adverse effects, including opportunistic infections, diabetes mellitus after transplantation, cardiovascular complications, and de novo malignancies. OBJECTIVES: To determine the short-term (12 months) cost-effectiveness of everolimus (EVR) versus mycophenolate sodium (MPS) in kidney transplant recipients receiving induction therapy, tacrolimus, prednisone, and no prophylaxis for cytomegalovirus infection. METHODS: A Markov state transition model was designed. Data from a single-center prospective trial were used along with data from the center's medical bills database. The target population comprised adults with low immunological risk submitted to first ABO-compatible transplantation with kidneys recovered from living or deceased donors. The time horizon was 12 months. The interventions included tacrolimus and prednisone plus a single 3-mg/kg dose of rabbit antithymocyte globulin (ATG) and EVR or basiliximab (BAS) and EVR or BAS and MPS. The clinical outcomes considered for this analysis were cytomegalovirus infection/disease, acute rejection, graft dysfunction, surgical complications, graft loss, and life-years gained. RESULTS: ATG/EVR was cost-saving compared with BAS/MPS on all evaluated outcomes; BAS/EVR outperformed BAS/MPS on most of the evaluated outcomes. Results were confirmed by sensitivity analysis. CONCLUSIONS: Compared with MPS, EVR is an alternative immunosuppressive agent that is able to provide resource-saving to the health care provider with effectiveness gains for the patient.