Improved treatment response with basiliximab immunoprophylaxis after liver transplantation: results from a double-blind randomized placebo-controlled trial.

Basiliximab, a high-affinity chimeric monoclonal antibody, is effective in reducing acute rejection episodes in renal allograft recipients. We assessed the ability of this antibody to similarly improve the outcome in liver transplant recipients. Adult recipients of a primary cadaveric liver transplant were randomized to treatment, stratified by hepatitis C virus (HCV) seropositivity. Patients were administered 40 mg of basiliximab (n = 188) or placebo (n = 193) as two 20-mg bolus injections days 0 and 4, plus cyclosporine and steroids. Primary efficacy variables were biopsy-confirmed acute rejection and its composite end point, including death or graft loss, and were assessed at 6 and 12 months and by HCV cohort. Because of differential efficacy responses between HCV-positive and HCV-negative cohorts, an additional analysis incorporating HCV recurrence as a component of treatment failure, termed problem-free transplant, was introduced. Safety and tolerability were monitored over the 12 months of the study. All 381 patients were assessable, and no meaningful differences in background characteristics were apparent between treatment groups. Biopsy-confirmed acute rejection rates 6 months after transplantation were 35.1% in the basiliximab group versus 43.5% in the placebo group. For death, graft loss, or first biopsy-confirmed acute rejection, rates were 44.1% versus 52.8%, respectively. The reduction in rejection episodes was concentrated in the HCV-negative cohort (14.5% relative to placebo; P =.034), with a much smaller difference (2.9%) in the HCV-positive cohort. For HCV-positive patients, problem-free transplant was shown at 12 months in 26.6% of the basiliximab group versus 11.6% in the placebo group (P =.020) and for all patients at 12 months in 39.7% of the basiliximab group versus 30.1% in the placebo group (P =.035). The incidence of infection and other adverse events was similar across the two treatment groups. There were 56 deaths (25 deaths, basiliximab group; 31 deaths, placebo group) over the 12-month study. The intravenous bolus injection was well tolerated. Immunoprophylaxis with 40 mg of basiliximab, in combination with cyclosporine and steroids, reduces the incidence of acute rejection episodes with no clinically relevant safety or tolerability concerns. The influence of HCV recurrence on efficacy results can be accounted for in future trials by using the concept of problem-free transplant, incorporating recurrence as a component of treatment failure.