Antithymocyte globulin (rabbit) - A review of the use of Thymoglobulin (R)(1) in the prevention and treatment of acute renal allograft rejection

The role of Thymoglobulin(R) (TMG), a polyclonal rabbit-derived antithymocy te globulin, in the prevention and treatment of acute renal allograft rejec tion is the focus of this review. TMG and the polyclonal horse-derived antithymocyte globulin Atgam(R) (ATG) have been compared in a multicentre double-blind, randomised study in 163 r enal 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 prim ary 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 dif ferences in Favour of TMG were seen in patients with moderately severe reje ction episodes. Recurrent episodes of rejection occurred significantly less often in patients who achieved the primary end-point and thus were less fr equent 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 te nded to be more effective than ATG, but the difference was not statisticall y significant. A pharmacoeconomic analysis of this trial suggests that trea tment with TMG is a cost saving strategy compared with ATG. In a small randomised trial TMG and muromonab-CD3 demonstrated similar effi cacy in patients with acute allograft rejection. TMG was more effective than ATG as induction immunosuppressive therapy in 7 2 adult renal allograft recipients in a comparative single centre study. Du ring 12 months of follow-up post-transplantation, the overall incidence of acute rejection episodes, a primary end-point, was significantly lower in p atients treated for greater than or equal to7 days with TMG 1.5 mg/kg/day t han 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 recei ved the drugs for induction therapy or as treatment of acute rejection. Imp ortantly, there was no significant difference in the frequency of infection in the: 2 groups. Indeed, the incidence of CMV disease was significantly l ower 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 re nal allograft rejection and appears to be superior to ATG when used as indu ction immunosuppressive therapy in renal transplantation. A pharmacoeconomi c analysis of the pivotal US study also suggests that there are cost benefi ts for TMG compared with ATG. Therefore, TMG is an effective alternative to ATG (and perhaps the currently available monoclonal preparation) and exten ds the choice of treatments for the management of acute renal allograft rej ection.