Randomized Double-Blind Study of Standard Versus Low-Dose OKT3 Induction Therapy in Renal Allograft Recipients

A double-blind, randomized, prospective study was undertaken to determine if the dose of OKT3 used for induction immunosuppression following kidney and kidney-pancreas transplantation affected clinical outcomes. Twenty-five patients were randomized in each group. Five patients in each group received a combined kidney/pancreas transplant. All patients received sequential quadruple immune suppression (azathioprine and methylprednisolone, followed by oral prednisone and cyclosporine A), regardless of randomization to the standard (5 mg) or low-dose (2 mg) OKT3 group. OKT3 was administered for 7 to 14 days. The dose of OKT3 was adjusted to ascertain the clearance of peripheral positive CD3 lymphocytes. The mean cumulative OKT3 dose for the standard dose group was 52.0 mg versus 23.4 mg for the low-dose group (P < 0.00001). Dosage increases were necessary for 29% of the standard dose and 32% of the low-dose patients. The side effect score for the standard versus low-dose group was not statistically different (0.79 ± 0.58 v 0.84 ± 0.68), except for chills, which occurred more frequently in the low-dose-treated patients (P = 0.003). Anti-OKT3 antibodies developed with similar frequency in both dosage groups, with 8% exhibiting titers of 1:500 or greater at the end of treatment. Kidney graft survival was 96% for the standard dose and 92% for the low-dose group. The overall incidence of rejection was similar in both groups; however the low-dose group did experience an increase in early rejection episodes. The incidence of major and minor viral and bacterial infections was also similar for both dosage groups. The mean creatinine levels for the standard versus low-dose groups at 1 month (1.8 v 2.03 mg/dL) and 6 months (1.48 v 1.62 mg/dL) were not significantly different between groups. This study demonstrates that low-dose OKT3 therapy, when administered in conjunction with sensitive immunologic monitoring, is successful in achieving adequate induction therapy.