Everolimus and reduced-exposure cyclosporine in de novo renal-transplant recipients: a three-year phase II, randomized, multicenter, open-label study.
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.
Nashan
Björn
B
Kliniken der med. Hochschule, Zentrum Chirurgie, Hannover, Germany. bjorn.nashan@cdha.nshealth.ca
Curtis
John
J
Ponticelli
Claudio
C
Mourad
Georges
G
Jaffe
Jonathan
J
Haas
Tomas
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000627:therapeutic use*; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus