Experience with daclizumab in liver transplantation: renal transplant dosing without calcineurin inhibitors is insufficient to prevent acute rejection in liver transplantation.
BACKGROUND
Daclizumab is a monoclonal antibody directed against the alpha chain of the interleukin 2 receptor. We review our experience with the use of daclizumab in liver transplant recipients.


METHODS
Thirty-two patients were given daclizumab as induction therapy in the setting of hepatic transplantation. Seven of these patients were enrolled in a pilot study to determine the efficacy of daclizumab in conjunction with corticosteroids and mycophenolate mofetil without the initial use of calcineurin inhibitors (CI). The remaining 25 patients received daclizumab, mycophenolate mofetil, and steroids, with the institution of CI generally within the first postoperative week. The majority of these patients (n = 17) had some degree of renal insufficiency.


RESULTS
The pilot study was halted after the first seven patients were enrolled because of an unacceptably high rate of rejection (7/7 = 100%). The patients outside of this pilot study, however, had a much lower rate of rejection (36%). The incidence and severity of rejection correlated with the delay in institution of CI. The described dosing schedule resulted in subtherapeutic daclizumab levels in liver transplant recipients.


CONCLUSIONS
Daclizumab used in liver transplant recipients without any CI was ineffective and can potentially lead to steroid-resistant rejection. The dosing regimen used in renal transplant recipients is most likely insufficient for liver transplant patients. However, daclizumab can be used safely in patients with preexisting or postoperative renal dysfunction in conjunction with low doses of CI given within the first week postoperatively.
Hirose
R
R
Department of Surgery, University of California, San Francisco 94143, USA.
Roberts
J P
JP
Quan
D
D
Osorio
R W
RW
Freise
C
C
Ascher
N L
NL
Stock
P G
PG
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D065095:Calcineurin Inhibitors; D002648:Child; D000077561:Daclizumab; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D016030:Kidney Transplantation; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010865:Pilot Projects; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000601:surgery; D016559:Tacrolimus / Q000627:therapeutic use
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D065095:Calcineurin Inhibitors; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus