Three-Year Outcomes in Kidney Transplant Patients Randomized to Steroid-Free Immunosuppression or Steroid Withdrawal, with Enteric-Coated Mycophenolate Sodium and Cyclosporine: The Infinity Study
In a six-month, multicenter, open-label trial, de novo kidney transplant recipients at low immunological risk were randomized to steroid avoidance or steroid withdrawal with IL-2 receptor antibody (IL-2RA) induction, enteric-coated mycophenolate sodium (EC-MPS: 2160？mg/day to week 6, 1440？mg/day thereafter), and cyclosporine. Results from a 30-month observational follow-up study are presented. Of 166 patients who completed the core study on treatment, 131 entered the follow-up study (70 steroid avoidance, 61 steroid withdrawal). The primary efficacy endpoint of treatment failure (clinical biopsy-proven acute rejection (BPAR) graft loss, death, or loss to follow-up) occurred in 21.4% (95% CI 11.8–31.0%) of steroid avoidance patients and 16.4% (95% CI 7.1–25.7%) of steroid withdrawal patients by month 36 ( ). BPAR had occurred in 20.0% and 11.5%, respectively ( ). The incidence of adverse events with a suspected relation to steroids during months 6–36 was 22.9% versus 37.1% ( ). By month 36, 32.4% and 51.7% of patients in the steroid avoidance and steroid withdrawal groups, respectively, were receiving oral steroids. In conclusion, IL-2RA induction with early intensified EC-MPS dosing and CNI therapy in de novo kidney transplant patients at low immunological risk may achieve similar three-year efficacy regardless of whether oral steroids are withheld for at least three months. 1. Introduction Steroid avoidance is now frequently attempted in de novo kidney transplant recipients at low immunological risk [1] to prevent the long-term complications associated with maintenance steroid therapy. Patients may be given only intravenous steroid administration at the time of transplant with no oral steroids at all or receive oral steroids for only a few days after transplant before withdrawal. A regimen that includes induction therapy, a calcineurin inhibitor (CNI), and mycophenolic acid (MPA) in patients who are not at high immunological risk appears to support such an approach without loss of efficacy [2–6], but minor increases in the rate of acute rejection have been reported [2]. In de novo kidney transplant patients receiving a standard regimen of steroids, use of an intensified MPA dosing regimen in the early after transplant period when the risk of rejection is the highest has been shown to reduce rejection [7, 8] prompting interest in early intensified MPA therapy when implementing a steroid avoidance strategy. The randomized, multicenter DOMINOS study compared a regimen in which patients were given no oral steroids versus a regimen of standard oral steroids
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