A combination of low doses of both everolimus and tacrolimus (EVR+rTAC) in de novo kidney transplant recipients may ease the wound healing problems observed in early studies involving high exposure to mTOR inhibitors, according to the findings of a prospective, randomized clinical trial presented at the 2023 American Transplant Congress in San Diego, California.
The trial, by Patrizia Silvestri, MD, of the Università Cattolica Sacro Cuore in Rome, Italy, and colleagues included 100 recipients randomly assigned to receive once-daily maintenance low-dose everolimus (3-5 ng/mL) plus reduced-exposure tacrolimus (3-5 ng/mL) or a standard regimen of tacrolimus plus mycophenolate mofetil. Both study arms received thymoglobulin for induction.
After a 5-year follow-up, the EVR+rTAC arm had a significantly lower acute rejection rate compared with the standard-regimen arm (3% vs 11%) as well as a significantly lower rate of cytomegalovirus infections (38% vs 70%), Dr Silvestri reported.
The investigators observed no significant differences in patient survival (93% in the EVR+rTAC arm and 91% in the standard-regimen arm), death-censored graft survival (96% and 95%, respectively), and renal function (54.6 and 49.6 mL/min/1.73 m2, respectively). They also found no significant difference in the rate of surgical complications within 30 days (20% and 17%, respectively) or in the severity of complications.
Dr Silvestri’s team concluded that their data demonstrate the safety and efficacy of long-term immunosuppression in kidney transplant recipients receiving EVR+rTAC. The data also indicate that the wound healing issues observed in early studies with high exposure to mTOR inhibitors can be prevented with reduced exposure to both everolimus and tacrolimus in combination.
Silvestri P, Spagnoletti G, Salerno M, Favi E, Zanoni N, Citterio F. Five years results of de novo kidney transplant recipients treated with the combination of low dose tacrolimus and everolimus: A prospective randomized clinical trial. Presented at: ATC 2023, San Diego, California, June 3-7. Abstract 227.