Randomized trial of rATg/Daclizumab vs. rATg/Alemtuzumab as dual induction therapy in renal transplantation: Results at 8years of follow-up

Transpl Immunol. 2017 Feb:40:42-50. doi: 10.1016/j.trim.2016.11.004. Epub 2016 Nov 22.

Abstract

Our goal in using dual induction therapy is to bring the kidney transplant recipient closer (through more effectively timed lymphodepletion) to an optimally immunosuppressed state. Here, we report long-term results of a prospective randomized trial comparing (Group I,N=100) rATG/Dac (3 rATG, 2 Dac doses) vs. (Group II,N=100) rATG/Alemtuzumab(C1H) (1 dose each), using reduced tacrolimus dosing, EC-MPS, and early corticosteroid withdrawal. Lower EC-MPS dosing was targeted in Group II to avoid severe leukopenia. Median follow-up was 96mo post-transplant. There were no differences in 1st BPAR (including borderline) rates: 10/100 vs. 9/100 in Groups I and II during the first 12mo(P=0.54), and 20/100 vs. 20/100 throughout the study(P=0.90). Equally favorable renal function was maintained in both treatment arms(N.S.). While not significant, more patients in Group II experienced graft loss, 25/100 vs. 18/100 in Group I(P=0.23). Actuarial patient/graft survival at 96mo was 92%/83% vs. 85%/73% in Groups I and II(N.S.). DWFG-due-to-infection(N.S.), EC-MPS withholding-due-to-leukopenia during the first 2mo(P=0.03), and incidence of viral infections(P=0.09) were higher in Group II, whereas EC-MPS withholding-due-to-GI symptoms was higher in Group I(P=0.009). No other adverse event differences were observed. While long-term anti-rejection and renal function efficacy were demonstrated in both treatment arms, slight over-immunosuppression of Group II patients occurred.

Keywords: Alemtuzumab; Biopsy-proven acute rejection; Daclizumab; Enteric-coated mycophenolate sodium; Graft survival; Rabbit antithymocyte globulin; Renal transplantation; Steroid avoidance; Tacrolimus.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Alemtuzumab / therapeutic use*
  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antilymphocyte Serum / therapeutic use*
  • Daclizumab
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Graft Rejection / drug therapy*
  • Graft Rejection / mortality
  • Graft Survival
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Immunosuppression Therapy
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation* / adverse effects
  • Lymphocyte Depletion
  • Male
  • Middle Aged
  • Prospective Studies
  • Rabbits
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antilymphocyte Serum
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Alemtuzumab
  • Daclizumab