Ten-year follow-up of a prospective, randomized trial of BT563/bb10 versus anti-thymocyte globulin as induction therapy after heart transplantation

Abstract

Background: Alloantigen-activated T cells express high-affinity interleukin-2 receptor (IL-2R). Specific blockade of this receptor has been associated with lower rejection episodes in clinical transplantation when compared with placebo. The first short-term results of the newer IL-2R antagonists are becoming available but little is known about the long-term effects of these drugs. The aim of the study was to compare the clinical efficacy of the IL-2R antagonist BT563 with polyclonal rabbit anti-thymocyte globulin (ATG) in heart transplant recipients.

Methods: Forty patients undergoing cardiac transplantation were randomly assigned to receive either BT563 or rabbit ATG as induction therapy, combined with triple immunosuppression thereafter. Ten-year surveillance for rejection, infection, allograft vasculopathy and tumorgenicity was performed. Allograft rejection and vasculopathy were assessed by endomyocardial biopsy and coronary angiography, respectively. Screening for infection included blood, urine or tracheobronchial cultures and serology.

Results: No difference was detected in terms of 10-year survival between the two groups (50% for the IL-2R group and 70% for the ATG group, p = 0.16). Actuarial incidence of severe rejection was significantly higher in the IL-2R group (55% vs 10% at 10 years post-operatively, p = 0.028; 55% vs 5% during the first month post-operatively, p = 0.0005). Patients receiving ATG had a higher incidence of viral infection. Freedom from allograft vasculopathy was significantly higher in the ATG group (80% vs 60%, p = 0.031).

Conclusions: BT563/BB10 is less effective than ATG for prevention of both acute allograft rejection and allograft vasculopathy after cardiac transplantation. Clinically relevant infections or tumorgenicity were not increased with the use of ATG.