A randomized exploratory trial of steroid avoidance in renal transplant patients treated with everolimus and low-dose cyclosporine

Background. Everolimus and cyclosporine exhibit synergistic immunosuppressive activity when given in combination. In this randomized trial, we explored whether the use of everolimus associated with low-dose cyclosporine could allow an early avoidance of steroids in de novo renal transplant recipients. Methods. In this exploratory multicenter trial, 65 out of 133 patients treated with basiliximab (days 0 and 4), everolimus 3 mg/day and cyclosporine were randomized to stop steroids on the seventh post-transplant day (group A), whereas the remaining 68 continued lowdose steroid treatment (group B). Results. During the follow-up, 30 patients of group A (46%) resumed steroids. According to the intention-totreat analysis, the 3-year graft survival rate was 95% in group A and 87% in group B (P ¼ ns). There were more biopsy-proven rejections in group A, the difference being of borderline significance (32% vs 18%; P ¼ 0.059). After 3 years, mean creatinine clearance was 52.3 � 17.1 ml/min in group A and 52.2 � 21.5 ml/min in group B. It was similar in the group A patients who experienced rejection (49.8 � 14.7 ml/min) and those who did not (53.6 � 18.3 ml/min; P ¼ 0.319). Mean serum cholesterol and triglyceride levels were, respectively, less than 250 mg/dl and less than 200 mg/dl in both groups, without any significant difference. Vascular thrombosis (0 vs 11.7%; P ¼ 0.0043) was more frequent in group B. Conclusions. Treatment based on everolimus and low-dose cyclosporine allowed excellent renal graft survival and stable graft function at 3 years. An early discontinuation of steroids increased the risk of acute rejection, but was associated with a better graft survival in the long-term. However, it was well tolerated only by 54% of patients.