New approaches to de novo immunosuppression and steroid elimination

Calcineurin inhibitors (CNIs) and steroids, the cornerstones of most immunosuppressive regimens over the past 20 years, have undesirable chronic side effects, leading to the application of new strategies with sirolimus (SRL) and mycophenolate mofetil (MMF). We evaluated de novo CNI avoidance and early steroid withdrawal among 145 renal recipients randomized to receive either SRL (n = 71) or cyclosporine (CsA; n = 74). All patients received polyclonal antithymocyte globulin (ATG) for 5 days, MMF, and steroid withdrawal at 6 months (SPIESSER study). At 12 months, patient and graft survivals, incidence of biopsy-proven acute rejection (BPAR), and rates of steroid withdrawal were not statistically different namely, 97% versus 97%; 90% versus 93%, 14.3% versus 8.6%, and 82.8% versus 84.1%, respectively. Among patients who remained on treatment according to the protocol, the estimated glomerular filtration rate (eGFR) was significantly higher with SRL (69 +/- 19 versus 60 +/- 14 mL/min; P < .01). In another study of delayed introduction of SRL, 192 renal recipients were prospectively randomized at week 12 to switch from CsA to SRL (n = 95) or to continue CsA (n = 97; CONCEPT study). At 12 months, patient and graft survivals of the randomized patients, incidence of BPAR, and rates of steroid withdrawal were not significantly different: 100% versus 100%, 100% versus 98%, 17% versus 8%, and 72% versus 78%, respectively. Upon ITT eGFR was significantly higher with SRL (68.9 vs 64.4 mL/min; P = .017). In both studies, a significant improvement in renal function was observed at 12 months among patients receiving a maintenance regimen with SRL plus MMF. Furthermore, steroids could be withdrawn in three quarters of the patients.