Reduction of acute renal allograft rejection by daclizumab

Background. Acute rejection is still a major problem in renal transplantati on and is one of the most important causes of chronic graft dysfunction and late graft loss. Selective immunosuppression with a humanized antibody aga inst the alpha-chain of the interleukin (IL)-2 receptor (CD25) was evaluate d to demonstrate the efficacy of this type of immunoprophylaxis in combinat ion with dual immunosuppression. Methods. We studied the effect of daclizumab, a humanized monoclonal antibo dy against the cu-chain of the IL-2 receptor, in a randomized double-blind, prospective phase III clinical trial in 275 patients receiving a first cad averic renal allograft. Among them 111 (83%) in the placebo arm and 116 (82 %) in the daclizumab arm received the full regimen of five doses (1.0 mg/kg ) every other week. Baseline immunosuppression consisted of cyclosporine an d corticosteroids. Results. At 6 months, 39 (28%) of the patients in the daclizumab group had biopsy-proven rejections, as compared with 63 (47%) in the placebo group (P =0.001). The need for additional antilymphocyte therapy, antithymocyte glob ulin, antilymphocyte globulin (ATG, ALG, OKT3) was also lower in the dacliz umab group (8% vs. 16%, P=0.02), and they required significantly lower mean (+/- SD) cumulative doses of prednisone (3750+/-1981 mg vs. 4438+/-2667 mg in the placebo group, P=0.01). Graft Function was significantly better (P= 0.02) in the daclizumab group (graft function rate: 58 vs. 51 ml/min, mean) as was patient survival (P=0.01, 99% vs. 94%). No specific adverse events were observed in daclizumab-treated patients. Patients receiving daclizumab experienced fewer cytomegalovirus infections (18% vs. 25%), and none died from severe infectious complications, compared to four patients in the plac ebo arm. No patient in the daclizumab group had a lymphoproliferative disor der or any other form of immunosuppression-related tumor during the first y ear after transplant. Conclusions. Administration of daclizumab in addition to dual immunosuppres sion therapy significantly reduced biopsy-proven acute rejection after rena l transplantation, improved patient survival, and did not add to the toxici ty of the immunosuppressive regimen.