Good Outcomes with Sirolimus Combinations in High-Risk Transplant Recipients

Sirolimus, given with either tacrolimus or cyclosporine, provides good one-year efficacy in high-risk renal allograft recipients, reports a trial in Transplantation.

The randomized, open-label, multicenter trial included 448 renal allograft recipients with risk factors for rejection: black race, nonprimary transplant, or high panel-reactive antibodies. They were assigned to sirolimus plus tacrolimus or sirolimus plus cyclosporine.

One-year efficacy failure rates were 22 percent with sirolimus-tacrolimus and 23 percent with sirolimus-cyclosporine. Acute rejection rates were 14 percent and 17 percent, respectively; graft survival was 90 percent in both groups. In patients receiving their assigned therapy, the glomerular filtration rate tended to be higher with sirolimus-tacrolimus.

Other one-year outcomes were similar between groups. Sirolimus-tacrolimus was associated with higher rates of diarrhea and herpes simplex. Other adverse events were more frequent with sirolimus-cyclosporine, including hypertension, calcineurin inhibitor toxicity, and increased creatinine.

It has been difficult to perform randomized trials evaluating outcomes in high-risk renal allograft recipients. This industry-sponsored study shows “equivalent benefit or risk” with the two sirolimus combinations studied, with no clear advantage of one regimen over the other [Gaber AO, Kahan BD, Van Buren C, Schulman SL, Scarola J, and Neylan JF, for the Sirolimus High-Risk Study Group: Comparison of sirolimus plus tacrolimus versus sirolimus plus cyclosporine in high-risk renal allograft recipients: results from an open-label, randomized trial. Transplantation 2008; 86:1187–1195].