Comparison of sirolimus plus tacrolimus versus sirolimus plus cyclosporine in high-risk renal allograft recipients: results from an open-label, randomized trial.
BACKGROUND
The efficacy and safety of sirolimus (SRL) plus tacrolimus (TAC) versus SRL plus cyclosporine (CsA) were compared in high-risk renal allograft recipients.


METHODS
Evaluable patients (448) were randomly assigned (1:1) before transplant to receive SRL+TAC or SRL+CsA with corticosteroids. Eligible patients were black and/or repeat transplant recipients, and/or those with high titer of panel-reactive antibodies.


RESULTS
Demographics were similar between groups. Both treatments demonstrated equivalent efficacy of the composite endpoint at 12 months with efficacy failure rates of 21.9% vs. 23.2% (SRL+TAC vs. SRL+CsA, respectively, 95% CI -10.0 to 7.1, P=0.737). Biopsy-confirmed acute rejection rate (13.8% vs. 17.4%) and graft survival rate (89.7% vs. 90.2%) were similar (SRL+TAC vs. SRL+CsA, respectively). In evaluable patients (received at least 1 dose of study drug), renal function (calculated Nankivell glomerular filtration rate) was not superior in SRL+TAC versus SRL+CsA (54.5 vs. 52.6 mL/min, P=0.466); however, in on-therapy patients, glomerular filtration rate was significantly higher in SRL+TAC at most time points. At 12 months, there were no significant differences in rates of death, discontinuation because of adverse events, hypercholesterolemia, hyperlipemia, or proteinuria. Diarrhea and herpes simplex infections occurred significantly more often in SRL+TAC patients. Hypertension, cardiomegaly, increased creatinine, overdose (primarily calcineurin inhibitor toxicity), acne, urinary tract disorders, lymphocele, and ovarian cysts occurred significantly more often in SRL+CsA patients.


CONCLUSIONS
This study demonstrated that SRL-based therapy was efficacious in high-risk renal allograft recipients in the first year after transplant, providing equivalent efficacy with CsA or TAC, similar graft survival, low biopsy-confirmed acute rejection rates, excellent renal function, and an acceptable safety profile.
Gaber
A Osama
AO
Methodist University Hospital, Memphis, TN, USA. aogaber@tmhs.org
Kahan
Barry D
BD
Van Buren
Charles
C
Schulman
Seth L
SL
Scarola
Joseph
J
Neylan
John F
JF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016572:Cyclosporine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D020123:Sirolimus / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous; D055815:Young Adult
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus