BACKGROUND: The microemulsion preconcentrate formulation of cyclosporine A (CsA) (Neoral) exhibits more uniform pharmacokinetics than the conventional formulation (Sandimmun; SIM). This randomized, open-label, U.K. multicenter study compared the efficacy, safety, and tolerability of Neoral and SIM in preventing acute rejection in de novo renal transplant recipients. METHODS:Adult cadaveric kidney recipients (n=293) receivedNeoral or SIM twice daily for 12 months. Initially identical Neoral and SIM doses were titrated, maintaining trough CsA levels within locally defined therapeutic limits. RESULTS: In the year after transplantation, acute rejection occurred in 34% of the Neoral and 47% of the SIM recipients (P=0.037). In the intent-to-treat population, fewer treatment failures (defined as acute rejection, graft loss, withdrawal, or death) occurred in the Neoral (45%) than the SIM recipients (58%) (P=0.015) and therapeutic CsA levels (> or =250 microg/L) were reached faster with Neoral than SIM (P=0.0017). Antibody treatment of refractory rejection was used slightly less in the Neoral group (Neoral: 10%; SIM: 12%). One-year patient and graft survival rates (excluding deaths with functioning grafts) were 95% and 88%, respectively, for Neoral and 96% and 89% for SIM. Both formulations were well tolerated. No differences were observed between therapies in the nature, frequency, or severity of adverse events. Neoral use was not associated with increased nephrotoxicity or excessive immunosuppression. CONCLUSIONS: Neoral reduced the incidence of acute rejection compared with SIM, without significant increases in adverse events. This was achieved without altering existing SIM protocols and was attributed to improved absorption of CsA from Neoral and less variability in whole blood CsA concentrations.
RCT Entities:
BACKGROUND: The microemulsion preconcentrate formulation of cyclosporine A (CsA) (Neoral) exhibits more uniform pharmacokinetics than the conventional formulation (Sandimmun; SIM). This randomized, open-label, U.K. multicenter study compared the efficacy, safety, and tolerability of Neoral and SIM in preventing acute rejection in de novo renal transplant recipients. METHODS: Adult cadaveric kidney recipients (n=293) received Neoral or SIM twice daily for 12 months. Initially identical Neoral and SIM doses were titrated, maintaining trough CsA levels within locally defined therapeutic limits. RESULTS: In the year after transplantation, acute rejection occurred in 34% of the Neoral and 47% of the SIM recipients (P=0.037). In the intent-to-treat population, fewer treatment failures (defined as acute rejection, graft loss, withdrawal, or death) occurred in the Neoral (45%) than the SIM recipients (58%) (P=0.015) and therapeutic CsA levels (> or =250 microg/L) were reached faster with Neoral than SIM (P=0.0017). Antibody treatment of refractory rejection was used slightly less in the Neoral group (Neoral: 10%; SIM: 12%). One-year patient and graft survival rates (excluding deaths with functioning grafts) were 95% and 88%, respectively, for Neoral and 96% and 89% for SIM. Both formulations were well tolerated. No differences were observed between therapies in the nature, frequency, or severity of adverse events. Neoral use was not associated with increased nephrotoxicity or excessive immunosuppression. CONCLUSIONS: Neoral reduced the incidence of acute rejection compared with SIM, without significant increases in adverse events. This was achieved without altering existing SIM protocols and was attributed to improved absorption of CsA from Neoral and less variability in whole blood CsA concentrations.
Authors: Anne-Kristina Frobel; Mats O Karlsson; Janne T Backman; Kalle Hoppu; Erik Qvist; Paula Seikku; Hannu Jalanko; Christer Holmberg; Ron J Keizer; Samuel Fanta; Siv Jönsson Journal: Br J Clin Pharmacol Date: 2013-10 Impact factor: 4.335