The evaluation of the safety and tolerability of two formulations of cyclosporine: Neoral and sandimmune - A meta-analysis

Background. Neoral, a microemulsion formulation of cyclosporine, was approv ed for use in the United States in 1995. Many studies comparing Neoral and Sandimmune have been conducted, and although most state that Neoral is the superior cyclosporine formulation, results have failed to conclusively demo nstrate this claim, The aim of this meta-analysis was to compare the safety and efficacy of Neoral and Sandimmune. Methods. Publications comparing the use of Neoral and Sandimmune were revie wed for demographic variables, adverse events, rejection incidence, graft l osses, and serum creatinine. Neoral and Sandimmune were compared hi all pat ients and in the following subgroups: (1) age (adult or pediatric), (2) tra nsplant type (kidney, liver, or heart), (3) indication (de novo or stable), and (4) study design (randomized prospective trials versus nonrandomized, blinded versus open-labeled studies). Results. The rate: of graft loss was similar when comparing Neoral anti San dimmune in all analyses. The incidence of rejection was lower in Neoral-tre ated de novo renal, liver, and cardiac transplants (P<0.05), There were sig nificantly more adverse events in Sandimmune-treated de novo liver transpla nts than Neoral-treated de novo liver transplants (P<0.00001). When conside ring only randomized prospective trials, the incidence of rejection was low er in Neoral-treated de novo and stable patients (P<0.05). However, there w ere more adverse events in Neoral-treated stable patients (P<0.00001). When considering only blinded studies, there were more adverse events in Neoral -treated patients (P<0.05), whereas in open-labeled studies there was Ilo d ifference in adverse events comparing Neoral and Sandimmune (P=NS). Conclusions. Considering all published trials, the data seem to indicate th at Neoral therapy is preferred because of a lower rejection incidence, with a trend toward less adverse events. However, when limiting the analysis to only randomized prospective trials, and specifically assessing blinded stu dies, the data become less clear. Neoral use was associated with more adver se events in blinded studies, and Sandimmune use was associated with more a dverse events in open-labeled studies. Careful individual consideration mus t be given in choosing the best possible cyclosporine formulation.