Combination therapy with everolimus and tacrolimus in kidney transplantation recipients: A systematic review

Background and aims: Immunosuppressive regimens are a key component for successful kidney transplantation. This systematic review aimed to assess the efficacy and safety of combination therapy of everolimus with tacrolimus in kidney transplantation recipients. Methods: Results were limited to English-language articles. Trials where recipients received another regimen were excluded. The Cochrane Central Register of Controlled Trials and MEDLINE were searched via the optimally sensitive strategies for the identification of randomized trials, combined with the following MeSH headings and text words: Everolimus, Certican, Zortress, tacrolimus, prograf, and kidney transplantation. Results: Five relevant studies of everolimus in combination with tacrolimus were identified and results of them were interpreted. Two trials investigated Fix dose of everolimus in combination with low (1.5-3 mg) versus standard dose of tacrolimus (4-7 mg). One trial investigated variable doses of everolimus (1.5 mg/day or 3 mg/day) in combination with fix dose of tacrolimusand two trials compared fix dose of everolimus versus reduction or elimination of tacrolimus. Sample size of RCTs ranged from 20 to 398 and the follow up time ranged from six to 24 months. The quality score on the Jadad score was 3 in all five trials indicating moderate quality. Conclusion: Immune suppressive regimens including everolimus in combination with tacrolimus therapy show better safety and efficacy compared with single-mode but these differences were not significant in overall studies. In general, compared with a regimen without combination of everolimus with tacrolimus, the newer immunosuppressive regimen consistently reduced the incidence of short-term biopsy-proven acute rejection. However, evidence about impact on side-effects, long term graft loss, compliance and overall health-related quality of life is limited.