NEORAL COMPARED TO SANDIMMUNE IS ASSOCIATED WITH A DECREASE IN HISTOLOGIC SEVERITY OF REJECTION IN PATIENTS UNDERGOING PRIMARY LIVER-TRANSPLANTATION

Background. In a randomized, controlled study we investigated the clin ical efficacy of the microemulsion formulation of cyclosporine (Neoral ) in comparison with Sandimmune (SIM) in the treatment of patients who underwent primary orthotopic liver transplantation (OLT). Methods. In total, 33 patients were randomized in a double-blind fashion before u ndergoing primary OLT to receive either Neoral or SIM. All 33 patients initially received intravenous cyclosporine, but as soon as it was to lerated, the oral study drug was initiated (median time, 3.6 days) and 17 patients received Neoral and 16 SIM (for both drugs, 10 mg/kg/day) . Both groups were comparable with regard to age, sex, etiology of chr onic liver disease, and hepatic biochemical profile. Episodes of rejec tion were diagnosed histologically and characterized as mild, moderate , or severe using criteria from the National Institute of Diabetes and Digestive and Kidney Diseases. Results. Patients were followed for 1 year. Four patients in each group were discontinued prematurely. The r eason for discontinuation of cyclosporine was drug-related complicatio ns in two of the NEO patients and in three of the SIM group; the other three were non-drug-related. Rejection episodes occurred in 9 of 17 p atients (52.9%) in the Neoral group and in 9 of 16 patients (56.3%) in the SLM group. The total number of rejection episodes in each group w as 14. However, in evaluating the severity of rejection histologically , nine episodes of rejection were characterized as moderate/severe in the SIM group compared with only three in the Neoral group (P=0.027). Five of the nine moderate/severe rejection episodes in the SIM group o ccurred within the first 2 weeks after transplant. In contrast, modera te/severe rejection did not occur in the Neoral group in this early pe riod. Two patients in the SIM group and no patients in the Neoral grou p required treatment with OKT3 for steroid-resistant rejection. There were no differences in mean doses or trough levels when comparing the two study groups. The incidence of adverse effects was similar in the two groups. Conclusions. Neoral is a safe and efficacious drug in the treatment of primary OLT patients. Given comparable doses of cyclospor ine in each group over 1 year, there was no significant difference in the total number of rejection episodes between study groups. However, patients treated with Neoral had a lower incidence of moderate/severe histologic rejection and were free of steroid-resistant rejection when compared with SIM-treated patients.