New Approaches to De Novo Immunosuppression and Steroid Elimination

Calcineurin inhibitors (CNIs) and steroids, the cornerstone of most immunosuppressive regimens in the past 20 years, have undesirable long-term side effects. This has led to the investigation of potential new strategies with sirolimus (SRL) and mycophenolate mofetil (MMF). In the SPIESSER study, de novo CNI avoidance and early steroid withdrawal were evaluated in 145 renal recipients randomized to receive either SRL (n = 71) or cyclosporine (CsA; n = 74). All patients received polyclonal anti-thymocyte globulin (ATG) for 5 days, MMF, and steroids withdrawn at 6 months. At 12 months, patient and graft survival, incidence of biopsy-proven acute rejection (BPAR), and rates of steroid withdrawal were not statistically different (97% vs 97%, 90% vs 93%, 14.3% vs 8.6%, and 82.8% vs 84.1%, respectively). In patients who remained on treatment according to the protocol, estimated glomerular filtration rate (eGFR) was significantly higher with SRL (69 +/- 19 vs 60 +/- 14 mL/min; P.01). In the CONCEPT study, early conversion from CsA to SRL was evaluated. One hundred ninety-two renal recipients were prospectively randomized at week 12 to switch from CsA to SRL (n = 95) or to continue CsA (n = 97). At 12 months, patient survival rates (100% vs 100%) and graft survival rates (100% vs 98%), incidence of acute rejection (17% vs 8%), and rates of steroid withdrawal (72% vs 78%) were not significantly different between the SRL and the CsA groups. eGFR was significantly higher with SRL (68.9 vs 64.4 mL/min; P = .017; intent-to-treat analysis). In both studies, a significant improvement in renal function was observed at 12 months in patients receiving a maintenance regimen with SRL and MMF. In addition, steroids could be withdrawn in 70% of these patients.