title: A multicenter, open-label, comparative trial of two daclizumab dosing strategies vs. no antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids for the prevention of acute rejection in simultaneous kidney-pancreas transplant recipients: interim analysis.
abstract: BACKGROUND
  The safety and efficacy of daclizumab (1 mg/kg/dose every 14 d for five doses) has been established in kidney and heart transplant recipients. Alternative dosing regimens based on pharmacokinetic simulation and limited clinical trials are being investigated. The purpose of this ongoing multicenter study is to determine the safety and efficacy of two dosing regimens of daclizumab as an adjunctive immunosuppressive agent compared with no antibody induction in simultaneous kidney-pancreas transplant (SKPT) recipients receiving tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids as primary immunosuppression.
  
  
  METHODS
  This is an interim report of a multicenter, prospective, open-label, randomized study with a target enrolment of 290 patients. Eligible SKPT patients were randomized to one of three groups: daclizumab 1 mg/kg/dose every 14 d for five doses (Group I), daclizumab 2 mg/kg/dose every 14 d for two doses (Group II), and no antibody induction (Group III). The primary endpoint of the study is a composite of the incidence of presumed or biopsy-proven kidney or pancreas rejection, graft loss, or death within the first 6 months post-transplantation.
  
  
  RESULTS
  A total of 166 patients were randomized into the three groups [Group I (n = 70), Group II (n = 74), Group III (n = 22)]. Demographic and transplant characteristics were similar among the groups. At a minimum follow-up of 3 months, patient, kidney and pancreas graft survival rates were similar among the three groups. However, the rates of acute renal allograft rejection were 18% (Group I), 8% (Group II), and 36% (Group III), p < 0.05. The probabilities of either kidney or pancreas allograft rejection were 22% (Group I), 8% (Group II), and 38% (Group III). At 3 months, the actuarial event-free survival (no acute rejection, allograft loss, or death) rates were 67, 81 and 50% in Groups I, II, and III, respectively. There were no differences in the incidence of infectious complications among the groups and no serious adverse events associated with daclizumab were observed.
  
  
  CONCLUSIONS
  The two-dose regimen (Group II) appears to be as effective as the five-dose regimen (Group I) in preventing acute rejection after SKPT and is associated with the lowest acute rejection rates and the highest rate of event-free survival (no rejection or graft loss). However, the benefits of daclizumab compared with no antibody induction await larger sample size accrual.
authors: Department of Surgery, University of Tennessee, Memphis 38163-2116, USA. rstratta@utmem.edu
authors: Robert J
authors: RJ
authors: Stratta
authors: Rita R
authors: RR
authors: Alloway
authors: Ernest
authors: E
authors: Hodge
authors: Agnes
authors: A
authors: Lo
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000517:prevention & control*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016035:Pancreas Transplantation / Q000276:immunology*; D011241:Prednisone / Q000008:administration & dosage*; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus