A randomized, double-blinded comparison of thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients.

Authors

Daniel C. Brennan, Washington University School of Medicine in St. LouisFollow
Karen Flavin, Washington University School of Medicine in St. Louis
Jeffrey A. Lowell, Washington University School of Medicine in St. LouisFollow
Todd K. Howard, Washington University School of Medicine in St. Louis
Surendra Shenoy, Washington University School of Medicine in St. Louis
Sandra Burgess, Washington University School of Medicine in St. Louis
Sara Dolan, Washington University School of Medicine in St. Louis
Jennifer M. Kano, Washington University School of Medicine in St. Louis
Mitchell Mahon, Washington University School of Medicine in St. Louis
Mark A. Schnitzler, Washington University School of Medicine in St. Louis
Robert Woodward, University of New Hampshire - Main Campus
William Irish, Washington University School of Medicine in St. Louis
Gary G. Singer, Washington University School of Medicine in St. Louis

Abstract

Abstract

Background. The aim of this study was to compare the efficacy and safety of Thymoglobulin (a rabbit-derived polyclonal antibody) to Atgam (a horse- derived polyclonal antibody) for induction in adult renal transplant recipients. Methods. Transplant recipients (n=72) were randomized 2:1 in a double-blinded fashion to receive Thymoglobulin (n=48) at 1.5 mg/kg intravenously or Atgam (n=24) at 15 mg/kg intravenously, intraoperatively, then daily for at least 6 days. Recipients were observed for at least 1 year of follow-up. Results. By 1 year after transplantation, 4% of Thymoglobulin- treated patients experienced acute rejection compared with 25% of Atgam- treated patients (P=0.014). The rate of acute rejection was lower with Thymoglobulin than Atgam (relative risk=0.09; P=0.009). Rejection was less severe with Thymoglobulin than Atgam (P=0.02). No recurrent rejection occurred with Thymoglobulin compared with 33% with Atgam (P=NS). Patient survival was not different, but the composite end point of freedom from death, graft loss, or rejection, the 'event-free survival,' was superior with Thymoglobulin (94%) compared with Atgam (63%; P=0.0905). Fewer adverse events occurred with Thymoglobulin (P=0.013). Leukopenia was more common with Thymoglobulin than Atgam (56% vs. 4%; P<0.0001) during induction. The mean absolute lymphocyte count remained below baseline with Thymoglobulin throughout the study (P<0.007), but with Atgam, significant lymphocyte reductions occurred only at day 7. The incidence of cytomegalovirus disease was less with Thymoglobulin than Atgam at 6 months (10% vs. 33%; P=0.025). Conclusions. Brief (7-day) induction with Thymoglobulin resulted in less frequent and less severe rejection, a better event-free survival, less cytomegalovirus disease, fewer serious adverse events, but more frequent early leukopenia than induction with Atgam. These results may in fact be explained by a more profound and durable beneficial lymphopenia.

Department

Health Management and Policy

Publication Date

4-1999

Journal Title

Transplantation

Publisher

Lippincott Williams & Wilkens

Digital Object Identifier (DOI)

10.1097/00007890-199904150-00013

Document Type

Article

Recommended Citation

Brennan, D.C., Flavin, K., Lowell, J.A., Howard, T.K., Shenoy, S., Burgess, S., Dolan, S., Kano, J.M., Mahon, M., Schnitzler, M.A., Woodward, R., Irish, W., Singer, G.G. A randomized, double-blinded comparison of thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients. (1999) Transplantation, 67 (7), pp. 1011-1018.

Rights

© 1999 Lippincott Williams & Wilkins, Inc.