A systematic review and meta-analysis comparing everolimus and calcineurin inhibitors (CNIs) to mycophenolate and CNIs in kidney transplant patients

BACKGROUND: This study compared everolimus and mycophenolate mofetil, each paired with calcineurin inhibitors (CNIs) and used with or without steroids, for maintaining immunosuppression in kidney transplant (KT) patients. METHODS: Relevant studies published before August 21, 2022 were retrieved from PubMed, the Cochrane Central Register of Controlled Trials, and the gray literature. The risk of bias was assessed independently using the revised Cochrane risk of bias assessment tool (RoB 2). RevMan ver. 5.4 was used to calculate the risk ratios (RRs) with corresponding 95% confidence intervals (CIs) for biopsy-proven acute rejection, death, and infection. The mean difference (MD) was used to compare the estimated glomerular filtration rate (eGFR) between the groups. RESULTS: Sixteen randomized controlled trials with a total of 5,403 patients were synthesized to compare everolimus (n=2,763) with mycophenolate (n=2,542) for maintaining post-KT immunosuppression. The meta-analysis showed no significant difference in the risk for biopsy-proven acute rejection (RR=1.12; 95% CI, 0.92–1.35; I(2)=29%) and death (RR=0.85; 95% CI, 0.63–1.16; I(2)=0%). The eGFR had no significant difference between the two groups (MD=0.93; 95% CI, −2.25 to 4.1; I(2)=84%). The risk for any infection was significantly higher in the mycophenolate group than in the everolimus group (RR=0.83; 95% CI, 0.73−0.93; I(2)=66%). CONCLUSIONS: Our meta-analysis showed that when paired with a CNI, everolimus and mycophenolate had no difference in risk for biopsy-proven acute rejection, death, or increase in eGFR. However, the mycophenolate group exhibited a significantly higher risk of infection.