Results of 3-year phase III clinical trials with daclizumab prophylaxis for prevention of acute rejection after renal transplantation.

Background. Daclizumab (Zenapax, Roche Pharmaceuticals), a humanized monocl onal antibody directed against the alpha chain of the interleukin 2 recepto r, has been shown to reduce the incidence of acute rejection at 6 months af ter renal transplantation in two phase III clinical trials. This report pre sents the combined land 3-year outcomes of kidney transplant recipients who participated in these two phase III clinical trials. Methods. Data from two multicenter, randomized, placebo-controlled trials w ere evaluated with regard to graft survival, patient survival, incidence of malignancies (including lymphoma), renal function (serum creatinine and gl omerular filtration rate [GFR]), and current maintenance immunosuppressive regimen. In addition, the impact of acute rejection and acute rejection req uiring treatment with antilymphocyte therapy upon 3-year graft survival was evaluated. Daclizumab was compared to placebo on a background of cyclospor ine (CsA), azathioprine, and corticosteroids (triple therapy, TT) or CsA an d corticosteroids (double therapy, DT). Results. Treatment with daclizumab in the pooled analysis demonstrated a si gnificant reduction in the incidence of biopsy-proven acute rejection episo des at 12 months posttransplant (43% vs. 28%, P <0.001). The 3-year graft s urvival was not significantly different between placebo and daclizumab-trea ted patients in the TT trial (83% vs. 84%) or in the DT trial (78% vs. 82%) . Pooled patient survival was excellent in both placebo- (91%) and daclizum ab- (93%) treated patients. The incidence of malignancies or posttransplant lymphoproliferative disorder (PTLD) in placebo- versus daclizumab-treated groups was comparable in both clinical trials. Renal function was similar b etween placebo- and daclizumab-treated groups in both the TT and DT trials. The occurrence of delayed graft function, acute rejection requiring antily mphocyte therapy at 6 months, and acute rejection at 12 months posttranspla nt were associated with decreased graft survival rates at 3 years posttrans plant. Conclusions. The beneficial effect of daclizumab prophylaxis upon the incid ence of acute rejection after renal transplant with TT or with DT was not a ssociated with adverse clinical sequelae, including the development of PTLD , at 3 years posttransplant. There was no beneficial effect of daclizumab o n graft survival at 3 years, but the trial was inadequately powered to dete ct this. Both studies showed excellent graft and patient survival at 3 year s.