Everolimus Plus Reduced‐Exposure CsA versus Mycophenolic Acid Plus Standard‐Exposure CsA in Renal‐Transplant Recipients

Everolimus allows calcineurin‐inhibitor reduction without loss of efficacy and may improve renal‐transplant outcomes. In a 24‐month, open‐label study, 833 de novo renal‐transplant recipients were randomized to everolimus 1.5 or 3.0 mg/day (target troughs 3–8 and 6–12 ng/mL, respectively) with reduced‐exposure CsA, or mycophenolic acid (MPA) 1.44 g/day plus standard‐exposure CsA. Patients received basiliximab ± corticosteroids. The primary endpoint was composite efficacy failure (treated biopsy‐proven acute rejection, graft loss, death or loss to follow‐up) and the main safety endpoint was renal function (estimated glomerular filtration rate [eGFR], by Modification of Diet in Renal Disease [MDRD]) at Month 12 (last‐observation‐carried‐forward analyses). Month 12 efficacy failure rates were noninferior in the everolimus 1.5 mg (25.3%) and 3.0 mg (21.9%) versus MPA (24.2%) groups. Mean eGFR at Month 12 was noninferior in the everolimus groups versus the MPA group (54.6 and 51.3 vs 52.2 mL/min/1.73 m² in the everolimus 1.5 mg, 3.0 mg and MPA groups, respectively; 95% confidence intervals for everolimus 1.5 mg and 3.0 mg vs MPA: ?1.7, 6.4 and ?5.0, 3.2, respectively). The overall incidence of adverse events was comparable between groups. The use of everolimus with progressive reduction in CsA exposure, up to 60% at 1 year, resulted in similar efficacy and renal function compared with standard‐exposure CsA plus MPA.