Review of combination therapy with mTOR inhibitors and tacrolimus minimization after transplantation

Abstract

We evaluated the efficacy and safety of immunosuppressive regimens containing a mammalian target of rapamycin (mTOR) inhibitor with tacrolimus (TAC) minimization therapy in solid organ transplant recipients. A PubMed search was conducted using the terms (mTOR OR sirolimus OR everolimus) AND tacrolimus AND renal AND (low OR reduced OR reduction OR minimization) AND transplant*; limited to title/abstract and English-language articles published from January 1, 2003, through January 28, 2013. Twenty-one relevant studies of TAC minimization therapy were identified and evaluated in the context of known concerns associated with immunosuppressive therapy. Review of these studies suggests that immunosuppressive regimens including an mTOR inhibitor and TAC minimization therapy better preserve renal function versus standard-dose TAC, without significant changes in patient survival or graft rejection rates. Among patients treated with an mTOR inhibitor plus TAC minimization therapy in 12 randomized controlled trials (n=856 kidney, n=190 heart, n=108 lung, n=719 liver patients), reported rates of infection (BK, cytomegalovirus, or Epstein-Barr virus) and malignancy were low (0% to 7%). Other adverse events were more commonly reported including dyslipidemia/hyperlipidemia in up to two thirds of patients, new-onset diabetes mellitus in up to 38%, wound complications in up to 22%, and hypertension in up to 17%.