Induction therapy after cardiac transplantation: a comparison of anti-thymocyte globulin and daclizumab in the prevention of acute rejection.
BACKGROUND
Induction therapy with antibodies decreases and delays early allograft rejection. We compared the safety and efficacy of daclizumab and anti-thymocyte globulin (ATG) with respect to the frequency and severity of acute cardiac allograft rejection in heart transplant recipients.


METHODS
Forty sequential adult patients were retrospectively studied. In the first 20 patients ATG (2.5 mg/kg daily for 3 to 5 days peri-/and post-operatively) was used as induction therapy and, in the remaining 20 patients, daclizumab (1 mg/kg peri-operatively and every 2 weeks thereafter for a total of 5 doses) was used. A standard triple-drug immunosuppression regimen was administered to all patients.


RESULTS
Baseline characteristics and trough levels of cyclosporine in the 2 groups were similar. During the induction period, defined as the first 3 months, 12 acute rejection episodes requiring treatment (ISHLT Grade > or =2) occurred in the ATG group and 9 in the daclizumab group (p > 0.05). However, the number of biopsies with Grade 1 rejection was increased >2-fold in the daclizumab group (n = 35) compared with the ATG group (n = 17; p = 0.04). The total number of biopsies performed within the first 3 months increased by 26% in the daclizumab group. The number and severity of rejection episodes after 3 months was similar in the 2 groups. The overall occurrence of bacterial infections was significantly higher in the ATG group than in the daclizumab group (p = 0.05).


CONCLUSIONS
ATG and daclizumab are equally effective in preventing acute rejections requiring treatment (ISHLT Grade > or =2). Due to the significantly greater frequency of Grade 1 rejections, daclizumab was found to be associated with an increased number of additional biopsies for monitoring rejection status. This implies additional costs to the transplant program, and the long-term implications of the increased number of low-grade rejection episodes remains to be determined.
Carlsen
Jørn
J
Medical Department B, Division of Cardiology, Rigshospitalet, Copehagen University Hospital, Copenhagen, Denmark. carlsen@rh.dk
Johansen
Martin
M
Boesgaard
Søren
S
Andersen
Claus B
CB
Arendrup
Henrik
H
Aldershvilet
Jan
J
Mortensen
Svend Aage
SA
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016572:Cyclosporine / Q000097:blood; D000077561:Daclizumab; D005260:Female; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000077561:Daclizumab