TY - JOUR
T1 - Everolimus and reduced-exposure cyclosporine in de novo renal-transplant recipients
T2 - A three-year phase II, randomized, multicenter, open-label study
AU - Nashan, Björn
AU - Curtis, John
AU - Ponticelli, Claudio
AU - Mourad, Georges
AU - Jaffe, Jonathan
AU - Haas, Tomas
PY - 2004/11/15
Y1 - 2004/11/15
N2 - Background. Everolimus and cyclosporine (CsA) exhibit synergistic immunosuppressive activity when used in combination. We explored the use of everolimus with a CsA-sparing strategy in de novo renal-transplant recipients. Methods. A phase II, randomized, open-label 3-year study was performed in 111 patients to compare the efficacy and tolerability of everolimus (3 mg/day) in combination with basiliximab, steroids, and either full-dose Neoral (FDN) or reduced-dose Neoral (RDN) (CsA trough levels 125-250 ng/mL and 50-100 ng/mL, respectively). Efficacy failure (biopsy-proven acute rejection, death, graft loss, or loss to follow-up), safety, and renal function were evaluated at 6, 12, and 36 months. A protocol amendment allowed further reduction of CsA exposure after 12 months. Results. Efficacy failure was significantly higher in FDN than in the RDN group at 6 (15.1% vs. 3.4%; P=0.046), 12 (28.3% vs. 8.6%; P=0.012), and 36 (35.8% vs. 17.2%; P=0.032) months. Mean creatinine clearance was higher in the RDN group at 6 (59.7 mL/min vs. 51.1 mL/min; P=0.009), 12 (60.9 mL/min vs. 53.5 mL/min; P=0.007), and 36 (56.6 mL/min vs. 51.7 mL/min; P=0.436) months. Discontinuations and serious adverse events were more frequent in the FDN group. Reduction of CsA exposure for 6 months during the amendment improved renal function in the FDN group. Conclusions. In de novo renal-transplant recipients, the regimen of everolimus plus RDN was well tolerated, with low efficacy failure and better renal function in comparison with everolimus plus FDN.
AB - Background. Everolimus and cyclosporine (CsA) exhibit synergistic immunosuppressive activity when used in combination. We explored the use of everolimus with a CsA-sparing strategy in de novo renal-transplant recipients. Methods. A phase II, randomized, open-label 3-year study was performed in 111 patients to compare the efficacy and tolerability of everolimus (3 mg/day) in combination with basiliximab, steroids, and either full-dose Neoral (FDN) or reduced-dose Neoral (RDN) (CsA trough levels 125-250 ng/mL and 50-100 ng/mL, respectively). Efficacy failure (biopsy-proven acute rejection, death, graft loss, or loss to follow-up), safety, and renal function were evaluated at 6, 12, and 36 months. A protocol amendment allowed further reduction of CsA exposure after 12 months. Results. Efficacy failure was significantly higher in FDN than in the RDN group at 6 (15.1% vs. 3.4%; P=0.046), 12 (28.3% vs. 8.6%; P=0.012), and 36 (35.8% vs. 17.2%; P=0.032) months. Mean creatinine clearance was higher in the RDN group at 6 (59.7 mL/min vs. 51.1 mL/min; P=0.009), 12 (60.9 mL/min vs. 53.5 mL/min; P=0.007), and 36 (56.6 mL/min vs. 51.7 mL/min; P=0.436) months. Discontinuations and serious adverse events were more frequent in the FDN group. Reduction of CsA exposure for 6 months during the amendment improved renal function in the FDN group. Conclusions. In de novo renal-transplant recipients, the regimen of everolimus plus RDN was well tolerated, with low efficacy failure and better renal function in comparison with everolimus plus FDN.
KW - Cyclosporine
KW - Everolimus
KW - Reduced exposure
KW - Renal transplantation
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UR - http://www.scopus.com/inward/citedby.url?scp=3943072739&partnerID=8YFLogxK
U2 - 10.1097/01.TP.0000140486.97461.49
DO - 10.1097/01.TP.0000140486.97461.49
M3 - Article
C2 - 15548972
AN - SCOPUS:3943072739
VL - 78
SP - 1332
EP - 1340
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 9
ER -