OKT3 for induction of immunosuppression and treatment of rejection in cardiac allograft recipients

Abstract

Following the initial reports in 1987 of the successful use of OKT3 in cardiac transplantation, a number of studies utilizing OKT3 for induction of immunosuppression and treatment of acute rejection have further confirmed its efficacy in the treatment of cardiac allografts. In clinical trials comparing OKT3 induction to conventional triple‐agent therapy with cyclosporine, azathioprine, and corticosteroids, OKT3 yielded significantly longer times to first rejection and lower percentages of patients with rejections in the 1st month following transplantation, even though, in the nonrandomized trials, OKT3 treatment was reserved for more high‐risk patients. In a number of studies comparing OKT3 to polyclonal antithymocyte globulins (ATG), OKT3 induction was followed by fewer rejection episodes/patient and a longer time to 1st rejection episode, although some trials reported more favorable results with ATG. The use of OKT3 for induction was shown to facilitate the withdrawal of maintenance corticosteroid therapy in significantly more patients than did ATG induction. Investigations give support to a 14‐day induction regimen with OKT3 in cardiac transplant recipients. Studies have shown successful retreatment with OKT3 following its use for induction and have indicated that low antibody titers are obtained with its initial use in most studies. Rescue treatment with OKT3 for acute rejection has successfully reversed rejection in a significantly higher percentage of patients than ATG. In one small trial, primary therapy with OKT3 reversed rejections in 100% of patients. As in other organ studies, first‐dose reactions accompanied the treatment of cardiac allografts in a majority of OKT3‐treated patients. A high incidence of lymphoproliferative disorder reported in one trial has not been replicated in other trials. Infection rates following OKT3 induction or treatment of rejection appeared to be similar to those following polyclonal antilymphocyte antibodies or standard triple‐drug therapy, although the incidence of infections varied considerably from investigation to investigation.