A randomized, controlled trial of everolimus-based dual immunosuppression versus standard of care in de novo kidney transplant recipients.

Kidney transplant recipients receiving calcineurin inhibitor-based immunosuppression incur increased long-term risks of cancer and kidney fibrosis. Switch to mammalian target of rapamycin (mTOR) inhibitors may reduce these risks. Steroid or Cyclosporin Removal After Transplant using Everolimus (SOCRATES), a 36-month, prospective, multinational, open-label, randomized controlled trial for de novo kidney transplant recipients, assessed whether everolimus switch could enable elimination of mycophenolate plus either steroids or CNI without compromising efficacy. Patients received cyclosporin, mycophenolate and steroids for the first 14 days then everolimus with mycophenolate and CNIwithdrawal (CNI-WD); everolimus with mycophenolate and steroid withdrawal (steroid-WD); or cyclosporin, mycophenolate and steroids (control). 126 patients were randomized. The steroid WD arm was terminated prematurely because of excess discontinuations. Mean eGFR at month 12 for CNI-WD versus control was 65.1 ml/min/1.73 m2 vs. 67.1 ml/min/1.73 m2 by ITT, which met predefined noninferiority criteria (P=0.026). The CNI-WD group experienced a higher rate of BPAR(31% vs. control 13%, P=0.048) and showed a trend towards higher composite treatment failure (BPAR, graft loss, death, loss to follow-up). The 12 month results from SOCRATES show noninferiority in eGFR, but a significant excess of acute rejection when everolimus was commenced at week 2 to enable a progressive withdrawal of mycophenolate and cyclosporin in kidney transplant recipients.

Enteric-coated mycophenolate sodium in combination with full dose or reduced dose cyclosporine, basiliximab and corticosteroids in Australian de novo kidney transplant patients.

AIM: Cyclosporine (CsA), dosed to achieve C2 targets, has been shown to provide safe and efficacious immunosuppression when used with a mycophenolate and steroids for de novo kidney transplant recipients. This study examined whether use of enteric-coated mycophenolate sodium (EC-MPS) together with basiliximab and steroids would enable use of CsA dosed to reduced C2 targets in order to achieve improved graft function. METHODS: Twelve-month, prospective, randomized, open-label trial in de novo kidney transplant recipients in Australia. Seventy-five patients were randomized to receive either usual exposure (n = 33) or reduced exposure (n = 42) CsA, EC-MPS 720 mg twice daily, basiliximab and corticosteroids. RESULTS: There was no significant difference in mean Cockcroft-Gault CrCl (creatinine clearance) (60.2 ± 17.6 mL/min per 1.73 m(2) vs 63.2 ± 24.3, P = 0.64 for usual versus reduced exposure respectively) at 6 months. There was no significant difference between treatment groups in the incidence of treatment failure defined as biopsy proven acute rejection, graft loss or death (secondary endpoint: 30.3% full exposure vs 35.7% reduced exposure). At 12 months the incidence of overall adverse events was the same in both groups. CONCLUSION: This exploratory study suggests de novo renal transplant patients can safely receive a treatment regimen of either full or reduced exposure CsA in combination with EC-MPS, corticosteroids and basiliximab, with no apparent difference in efficacy or graft function during the first year after transplant.

Conversion to enteric-coated mycophenolate sodium from mycophenolate mofetil in stable renal transplant patients: results of an Asia-Pacific study.

AIM: Mycophenolate mofetil has proven efficacy in the prophylaxis of acute rejection in solid organ transplantation; however, gastrointestinal intolerance can risk this efficacy because of associated dose adjustments and discontinued treatment. Enteric-coated mycophenolate sodium has demonstrated improved gastrointestinal tolerability, but the data in Asian subjects are scarce. METHODS: This was a Phase-IIIb, open-label, single-arm, multicentre, prospective 6-month study which investigated safety and graft function in stable maintenance renal transplant recipients of Asian origin, after switching from mycophenolate mofetil to enteric-coated mycophenolate sodium at least 3 months after transplantation. Primary end-points included renal allograft function and safety parameters. RESULTS: The study recruited patients from 16 centres in Asian countries. The intention-to-treat and safety populations both included 122 patients. Graft function remained stable over the course of the study as measured by creatinine clearance and glomerular filtration rate. At 6 months the incidence of any gastrointestinal adverse events was 20.5% (n = 25), none of which required dose adjustments. There were only three cases of biopsy proven acute rejection with no reports of graft loss or death. CONCLUSION: This study demonstrated that enteric-coated mycophenolate sodium is a safe and effective alternative to mycophenolate mofetil in Asian kidney transplant recipients.