Prevention of rejection in cardiac transplantation by blockade of the interleukin-2 receptor with a monoclonal antibody.

Background: Alloantigen-activated T cells express the high-affinity interle ukin-2 receptor. Specific blockade of this receptor with the human IgG1 mon oclonal antibody daclizumab may prevent rejection of allografts after cardi ac transplantation without inducing global immunosuppression. Methods: We randomly assigned 55 nonsensitized patients undergoing a first cardiac transplantation to receive either induction therapy with daclizumab (1.0 mg per kilogram of body weight), given intravenously within 24 hours after cardiac transplantation and every two weeks thereafter, for a total o f five doses, or generalized immunosuppressive therapy. Concomitant immunos uppression was achieved in both groups with cyclosporine, mycophenolate mof etil, and prednisone. The primary end points were the incidence and severit y of acute rejection, and the length of time to a first episode of biopsy-c onfirmed rejection. Results: Of the 55 patients in the study, 28 were randomly assigned to rece ive daclizumab and 27 served as the control group. During induction therapy , the mean frequency of acute rejection episodes (defined as a histologic g rade of 2 or higher according to the classification of the International So ciety of Heart and Lung Transplants) was 0.64 per patient in the control gr oup and 0.19 per patient in the daclizumab group (P=0.02). Acute rejection developed in 17 of 27 patients in the control group (63 percent), as compar ed with 5 of 28 patients in the daclizumab group (18 percent; relative risk , 2.8; 95 percent confidence interval, 1.1 to 7.4; P=0.04). Throughout foll ow-up, there were nine patients with episodes of acute rejection of histolo gic grade 3 in the control group, as compared with two in the daclizumab gr oup (P=0.03), and the time to a first episode of rejection was significantl y longer in the daclizumab group (P=0.04). There were no adverse reactions to daclizumab and no significant differences between the groups in the inci dence of infection or cancer during follow-up. Conclusions: Induction therapy with daclizumab safely reduces the frequency and severity of cardiac-allograft rejection during the induction period. ( N Engl J Med 2000;342:613-9.) (C)2000, Massachusetts Medical Society.