A randomized trial of thymoglobulin vs. alemtuzumab (with lower dose maintenance immunosuppression) vs. daclizumab in renal transplantation at 24 months of follow-up.

INTRODUCTION: A long-term prospective randomized trial evaluating alemtuzumab, a humanized anti-CD52 monoclonal antibody, in a predominantly non-Caucasian population has yet to be reported. METHODS: Ninety deceased donor (DD) first renal transplant recipients were randomized into three different antibody induction groups: group A, thymoglobulin (Thymo); group B, alemtuzumab; group C, daclizumab (Dac). In groups A and C, the target trough levels of tacrolimus were 8-10 ng/mL, mycophenolate mofetil (MMF) 1 g administered twice daily, and maintenance methylprednisolone. In group B, target tacrolimus trough levels were 4-7 ng/mL, 500 mg MMF administered twice-daily, without methylprednisolone. African-Americans and Hispanics comprised more than 50% in each group. RESULTS: A minimum follow-up of 27 months showed no overall group differences in patient or graft survival (p = 0.89 and 0.66), but a trend towards worse death-censored graft survival in group B (p = 0.05). Acute rejection rates were not significantly different: six (20%), seven (23%), and seven (23%) in groups A, B, and C, respectively. The incidence of chronic allograft nephropathy was higher in group B than in A and C (p = 0.008). The mean calculated creatinine clearance at 24 months was 81.1 +/- 5.5, 64.4 +/- 4.5, and 80.7 +/- 5.7 in groups A, B, and C, respectively (p = 0.01 for B vs. average of A and C). CONCLUSION: In this randomized 27-month minimum follow-up trial of predominantly non-Caucasian DD renal transplant recipients with alemtuzumab induction, lower maintenance tacrolimus, MMF, and steroid avoidance appear less effective than either Thymo or Dac with higher maintenance immunosuppression.

A randomized trial of three renal transplant induction antibodies: early comparison of tacrolimus, mycophenolate mofetil, and steroid dosing, and newer immune-monitoring.

BACKGROUND: New trends in immunosuppression in clinical transplantation include the use of antibody induction agents in protocols that emphasize reduction or avoidance of steroids and calcineurin inhibitors. METHODS: In a randomized trial using three different antibody induction agents in 90 first renal transplant recipients from cadaver donors, group A received Thymoglobulin, group B received Alemtuzumab, and group C received Daclizumab. Maintenance immunosuppression included tacrolimus and mycophenolate in all three arms, and methylprednisolone in groups A and C only (standard clinical institutional practice). The targeted trough level of tacrolimus was between 8 and 10 ng/mL for groups A and C, respectively, with a targeted mycophenolate dose of 1 g twice daily. However, in group B, the target tacrolimus trough level was 4 to 7 ng/mL to reduce long-term nephrotoxicity, with 500 mg twice-daily doses of mycophenolate, without steroid maintenance. RESULTS: In this 15-month median postoperative interval report, there were no notable differences in demographics and patient and graft survivals. Acute rejection rates at 1 year were equivalent, that is, 5 of 30 in all three groups (16.6%). In group B, there was slightly lower renal function at 1 month, but no difference at 1 year. There was also significantly more leukopenia, but a greater percentage of T-regulatory cells and number of Fox-P3 mRNA copies by flow cytometry and semiquantitative polymerase chain reaction analysis, respectively, in group B. CONCLUSIONS: This preliminary analysis indicates that 80% of the patients in group B remained steroid-free 1 year postoperatively, with lower tacrolimus trough levels and no difference in other adverse events.