Antithymocyte Globulin (Rabbit)

Abstract

Abstract The role of Thymoglobulin® (TMG), a polyclonal rabbit-derived antithymocyte globulin, in the prevention and treatment of acute renal allograft rejection is the focus of this review. TMG and the polyclonal horse-derived antithymocyte globulin Atgam® (ATG) have been compared in a multicentre double-blind, randomised study in 163 renal allograft recipients who were experiencing acute rejection. TMG 1.5 mg/kg/day was significantly more effective than ATG 15 mg/kg/day for the primary end-point (88 vs 76%; return of serum creatinine to baseline at the end of therapy or within 14 days of initiation of treatment). The greatest differences in favour of TMG were seen in patients with moderately severe rejection episodes. Recurrent episodes of rejection occurred significantly less often in patients who achieved the primary end-point and thus were less frequent in recipients of TMG than ATG. For a composite end-point, return of serum creatinine to baseline and a functioning allograft at 30 days, TMG tended to be more effective than ATG, but the difference was not statistically significant. A pharmacoeconomic analysis of this trial suggests that treatment with TMG is a cost saving strategy compared with ATG. In a small randomised trial TMG and muromonab-CD3 demonstrated similar efficacy in patients with acute allograft rejection. TMG was more effective than ATG as induction immunosuppressive therapy in 72 adult renal allograft recipients in a comparative single centre study. During 12 months of follow-up post-transplantation, the overall incidence of acute rejection episodes, a primary end-point, was significantly lower in patients treated for ≥7 days with TMG 1.5 mg/kg/day than ATG 15 mg/kg/day (4 vs 25%). TMG is also used for induction therapy in corticosteroid-free immunosuppressive regimens. Leucopenia occurred in significantly more TMG than ATG recipients who received the drugs for induction therapy or as treatment of acute rejection. Importantly, there was no significant difference in the frequency of infection in the 2 groups. Indeed, the incidence of CMV disease was significantly lower among TMG-than ATG-treated patients (12.5% vs 33.3%) during 1 year of follow-up after induction therapy with either agent. Conclusions: TMG is at least equivalent to ATG for the reversal of acute renal allograft rejection and appears to be superior to ATG when used as induction immunosuppressive therapy in renal transplantation. A pharmacoeconomic analysis of the pivotal US study also suggests that there are cost benefits for TMG compared with ATG. Therefore, TMG is an effective alternative to ATG (and perhaps the currently available monoclonal preparation) and extends the choice of treatments for the management of acute renal allograft rejection.