Search

The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years postrandomization (mean: 5.6 years) was attended by 72/140 everolimus patients (51.4%) and 91/142 controls (64.1%). Mean measured GFR remained stable in the everolimus group from randomization (51.3 ml/min) to last visit (51.4 ml/min) but decreased in controls (from 50.5 ml/min to 45.3 ml/min) and was significantly higher with everolimus at last follow-up ( P = 0.004). The least squares mean (SE) change from randomization was −1.5 (1.7)ml/min with everolimus versus −7.2 (1.7)ml/min for controls (difference: 5.7 [95% CI 1.7; 9.6]ml/min; P = 0.006). The difference was accounted for by heart transplant patients (difference: 6.9 [95% 2.3; 11.5]ml/min; P = 0.004). Lung transplant patients showed no between-group difference at last follow-up. Rates of rejection, death, and major cardiac events were similar between groups, as was graft function. Pneumonia was more frequent with everolimus (18.3% vs. 6.4%). In conclusion, introducing everolimus in maintenance heart transplant patients, with reduced CNI, achieves a significant improvement in renal function which is maintained for at least 5 years, but an early renal benefit in lung transplant patients was lost. Long-term immunosuppressive efficacy was maintained. [ABSTRACT FROM AUTHOR]

In a single-center study, 20 kidney transplant patients without prior rejection were abruptly converted from cyclosporine to everolimus at seven wk post-transplant. All patients received basiliximab induction with maintenance enteric-coated mycophenolate sodium and corticosteroids. Biopsy-proven acute rejection had occurred in three of 20 patients (15.0%) by the end of week seven post-conversion. All episodes were mild and reversible, with subsequent recovery of renal function. Calculated glomerular filtration rate (GFR) improved significantly (51 ± 11 mL/min at time of conversion, 58 ± 12 mL/min at week seven post-conversion, 57 ± 17 mL/min at month six post-conversion; p = 0.001). No patient developed proteinuria in the nephrotic range. Twenty-two adverse events were reported in 10 patients, three of which had a suspected relationship to everolimus. Mean leukocyte and platelet count decreased significantly, and triglyceride level increased. This study suggests that kidney transplant patients without prior rejection can be converted abruptly from cyclosporine to everolimus at seven wk post-transplant, resulting in significantly improved renal function with no apparent increase, in risk of rejection and good tolerability. [ABSTRACT FROM AUTHOR]

Lorber MI, Ponticelli C, Whelchel J, Mayer HW, Kovarik J, Li Y, Schmidli H. Therapeutic drug monitoring for everolimus in kidney transplantation using 12-month exposure, efficacy, and safety data.Clin Transplant 2005 DOI: 10.1111/j.1399–0012.2005.00326.x© Blackwell Munksgaard, 2005The aims of the current study were to determine whether therapeutic drug monitoring (TDM) might benefit kidney transplant recipients receiving everolimus, and to establish dosage recommendations when everolimus is used in combination with cyclosporine and corticosteroids. The analysis was based on data from 779 patients enrolled in two 12-month trials. Everolimus trough concentrations≥3 ng/mL were associated with a reduced incidence in biopsy-proven acute rejection (BPAR) in the first month (p = 0.0001) and the first 6 months (p = 0.0001), and reduced graft loss compared with lower concentrations (4% vs. 20%, respectively). By contrast, cyclosporine in the standard concentration range had no impact on BPAR within the same timeframes. Most patients receiving everolimus 1.5 or 3 mg/d achieved trough concentrations above the therapeutic threshold of 3 ng/mL, regardless of reductions in cyclosporine dose. TDM simulation showed that just two dose adjustments would achieve median everolimus trough values≥3 ng/mL in 95% of patients during the first 6 months.This investigation indicates that improved efficacy is likely when TDM is considered as an integral component of the immunosuppressive strategy of everolimus. [ABSTRACT FROM AUTHOR]

An economic evaluation was undertaken alongside a multi-centre, international, trial of everolimus (Certican). Resource usage within the trial was assessed, and the cost implications of the use of everolimus were evaluated. Recipients of a primary cadaveric kidney transplant were recruited into a double-blind trial and received either everolimus 1.5 mg (n = 194); everolimus 3 mg (n = 198) or mycophenolate mofetil (MMF) 2 g (n = 196). Clinical outcomes and resource usage were monitored for 12 months following transplantation. Local costs were obtained, and global analysis using health sector PPP rates was undertaken. The mean overall cost of treatment was $33,715 (95%CI $30,013-$37,417) with everolimus 1.5 mg, $38,519 (95%CI $34,094- $42,943) with everolimus 3 mg and $36,509 (95%CI $32,430-$40,587) with MMF. Differences between the three groups did not reach statistical significance. In conclusion, the economic analysis showed statistical equivalence over the three arms of the trial. Further work is required to demonstrate the cost consequences of the use of everolimus compared with MMF in renal transplantation patients. [ABSTRACT FROM AUTHOR]