title: Results of 3-year phase III clinical trials with daclizumab prophylaxis for prevention of acute rejection after renal transplantation.
abstract: BACKGROUND
  Daclizumab (Zenapax, Roche Pharmaceuticals), a humanized monoclonal antibody directed against the alpha chain of the interleukin 2 receptor, has been shown to reduce the incidence of acute rejection at 6 months after renal transplantation in two phase III clinical trials. This report presents the combined 1- and 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 were evaluated with regard to graft survival, patient survival, incidence of malignancies (including lymphoma), renal function (serum creatinine and glomerular filtration rate [GFR]), and current maintenance immunosuppressive regimen. In addition, the impact of acute rejection and acute rejection requiring treatment with antilymphocyte therapy upon 3-year graft survival was evaluated. Daclizumab was compared to placebo on a background of cyclosporine (CsA), azathioprine, and corticosteroids (triple therapy, TT) or CsA and corticosteroids (double therapy, DT).
  
  
  RESULTS
  Treatment with daclizumab in the pooled analysis demonstrated a significant reduction in the incidence of biopsy-proven acute rejection episodes at 12 months posttransplant (43% vs. 28%, P<0.001). The 3-year graft survival was not significantly different between placebo and daclizumab-treated 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 daclizumab- (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 between placebo- and daclizumab-treated groups in both the TT and DT trials. The occurrence of delayed graft function, acute rejection requiring antilymphocyte therapy at 6 months, and acute rejection at 12 months posttransplant were associated with decreased graft survival rates at 3 years posttransplant.
  
  
  CONCLUSIONS
  The beneficial effect of daclizumab prophylaxis upon the incidence of acute rejection after renal transplant with TT or with DT was not associated with adverse clinical sequelae, including the development of PTLD, at 3 years posttransplant. There was no beneficial effect of daclizumab on graft survival at 3 years, but the trial was inadequately powered to detect this. Both studies showed excellent graft and patient survival at 3 years.
authors.affiliation: Division of Transplantation, Department of Surgery, The Ohio State University and Medical Center, Columbus, Ohio 43210-1250, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Bumgardner
authors.forename: I
authors.initials: I
authors.lastname: Hardie
authors.forename: R W
authors.initials: RW
authors.lastname: Johnson
authors.forename: A
authors.initials: A
authors.lastname: Lin
authors.forename: B
authors.initials: B
authors.lastname: Nashan
authors.forename: M D
authors.initials: MD
authors.lastname: Pescovitz
authors.forename: E
authors.initials: E
authors.lastname: Ramos
authors.forename: F
authors.initials: F
authors.lastname: Vincenti
mesh_terms: D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D001379:Azathioprine / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D000077561:Daclizumab; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality / Q000502:physiology; D008232:Lymphoproliferative Disorders / Q000209:etiology; D009369:Neoplasms / Q000209:etiology; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D016572:Cyclosporine; D000077561:Daclizumab; D001379:Azathioprine