Dadizumab - A review of its use in the management of organ transplantation

The humanised monoclonal antibody daclizumab is an immunosuppressive agent that reduces acute rejection in solid organ transplantation. It is specific for the a subunit (Tac/CD25) of the interleukin (IL)-2 receptor on activated T cells and achieves immunosuppression by competitive antagonism of IL-2-induced T cell proliferation. When added to standard triple immunosuppression regimens, daclizumab significantly reduces the rate of acute rejection at 1 year in renal transplantation by 36% and there are indications that it may be effective in other solid organ transplantations. Three-year outcomes of two phase III clinical trials in renal transplantation indicate similar values for graft and patient survival between daclizumab and placebo when given in addition to triple immunosuppression; however, these pivotal trials were not designed with sufficient power to demonstrate any statistical significance. The addition of daclizumab induction shows potential in allowing calcineurin inhibitor- and corticosteroid-sparing regimens without increasing the rate of acute graft rejection or adverse effects in renal and liver transplantation. Preliminary reports indicate that daclizumab may also be a useful agent in delayed graft function and graft versus host disease (GVHD). Further investigation of its efficacy in these group., and in children is needed. Data from clinical trials show daclizumab to be well tolerated in solid organ transplantation. It does not increase the incidence of (i)nfection, including cytomegalovirus infection, when compared with placebo or no induction groups. Preliminary comparative data with muromonab CD3 indicate that daclizumab may be associated with a lower rate of infectious complications and similar or better efficacy. Conclusions: In conclusion, daclizumab has been proven to reduce acute rejection in renal transplant recipients when given in addition to traditional base-line immunosuppression. It has shown potential to reduce acute rejection in other solid organ transplants; however, well designed, randomised studies are required to confirm this. Clinical experience from trials to date indicate that daclizumab has a tolerability profile similar to placebo with no significant effect on the incidence of infection. The relative efficacy and tolerability of daclizumab compared with other induction agents has yet to be defined. Available data suggest that daclizumab may allow the use of calcineurin inhibitor-sparing and corticosteroid-sparing regimens and may have potential in the treatment of GVHD.