Steroid avoidance with early intensified dosing of enteric-coated mycophenolate sodium: a randomized multicentre trial in kidney transplant recipients

Abstract

Short-term intensified dosing using enteric-coated mycophenolate sodium (EC-MPS) reduces rejection after kidney transplantation without compromising safety and may facilitate steroid avoidance. In a 6-month, multicentre open-label trial, 222 de novo kidney transplant recipients at low-immunological risk were randomized to steroid avoidance or maintenance steroids with interleukin (IL)-2 receptor antibody (IL-2RA) induction, EC-MPS (2160 mg/day to Week 6, 1440 mg/day thereafter) and cyclosporine. The primary end point; treatment failure at Month 6 [biopsy-proven acute rejection (BPAR), graft loss, death or loss to follow-up], occurred in 17.9% (20/112) of steroid-avoidance patients and 14.5% (16/110) of controls (difference 3.4%, 95% confidence interval -6.3 to 13.1, P = 0.47 for superiority testing). BPAR occurred in 11.6 and 7.3% of patients in the steroid-avoidance and control arms, respectively (P = 0.27). Creatinine clearance was similar at Month 6 (steroid-avoidance 56 ± 18 mL/min/1.73 m(2), controls 60 ± 22 mL/min/1.73 m(2), P = 0.34). Cytomegalovirus infection, as reported by investigators, occurred in 12.5% of steroid-avoidance patients and 22.7% of controls (P = 0.045). A regimen of early intensified EC-MPS dosing with calcineurin inhibitor and IL-2RA induction permits oral steroid avoidance in adult kidney transplant patients at low-immunological risk without compromising efficacy at 6 months' follow-up.